Compartmentation: Cells and Tissues

Functional Compartments of the Body 3 The Lumens of Some Organs Are Outside the Body Functionally, the Body Has Three Fluid Compartments Biological Membranes The Cell Membrane Separates Cell from Environment Membranes Are Mostly Lipid and Protein Membrane Lipids Create a Hydrophobic Barrier Membrane Proteins May Be Loosely or Tightly Bound to the Membrane Membrane Carbohydrates Attach to Both Lipids and Proteins Intracellular Compartments Cells Are Divided into Compartments The Cytoplasm Includes Cytosol, Inclusions, Fibers, and Organelles Inclusions Are in Direct Contact with the Cytosol Cytoplasmic Protein Fibers Come in Three Sizes Microtubules Form Centrioles, Cilia, and Flagella The Cytoskeleton Is a Changeable Scaff old Motor Proteins Create Movement Organelles Create Compartments for Specialized Functions The Nucleus Is the Cell’s Control Center Tissues of the Body Extracellular Matrix Has Many Functions Cell Junctions Hold Cells Together to Form Tissues Epithelia Provide Protection and Regulate Exchange Connective Tissues Provide Support and Barriers Muscle and Neural Tissues Are Excitable

Cells are organisms, Tissue Remodeling and entire animals Apoptosis Is a Tidy Form of Cell Death and plants are Stem Cells Can Create New Specialized Cells aggregates of these Organs organisms. Focus on … The Skin —Theodor Schwann, 1839

Background Basics Compartmentation Extracellular fl uid Hydrophobic molecules Proteins p H Covalent and noncova- lent interactions Pancreas cell

66 Compartmentation: Cells and Tissues

hat makes a compartment? We may think of some- example is the intracellular compartment called the lysosome , thing totally enclosed, like a room or a box with a with an internal pH of 5 . Th is pH is so acidic that if the lyso- W lid. But not all compartments are totally enclosed . . . some ruptures, it severely damages or kills the cell that contains think of the modular cubicles that make up many modern it. workplaces. And not all functional compartments have walls . . . Th e disadvantage to compartments is that barriers between think of a giant hotel lobby divided into conversational group- them can make it diffi cult to move needed materials from one ings by careful placement of rugs and furniture. Biological com- compartment to another. Living organisms overcome this prob- partments come with the same type of anatomic variability, lem with specialized mechanisms that transport selected sub- ranging from totally enclosed structures such as cells to func- stances across membranes. tional compartments without visible walls. In this chapter we explore the theme of compartmentation The first living compartment was probably a simple cell by fi rst looking at the various compartments that subdivide the whose intracellular fl uid was separated from the external envi- human body, from body cavities to the subcellular compart- 3 ronment by a wall made of phospholipids and proteins—the cell ments called organelles. We then examine how groups of cells membrane. Cells are the basic functional unit of living organ- with similar functions unite to form the tissues and organs of the isms, and an individual cell can carry out all the processes of life. body. Continuing the theme of molecular interactions, we also As cells evolved, they acquired intracellular compartments look at how diff erent molecules and fi bers in cells and tissues separated from the intracellular fl uid by membranes. Over time, give rise to their mechanical properties: their shape, strength, groups of single-celled organisms began to cooperate and spe- fl exibility, and the connections that hold tissues together. cialize their functions, eventually giving rise to multicellular organisms. As multicellular organisms evolved to become larger and more complex, their bodies became divided into various Functional Compartments functional compartments. of the Body Compartments are both an advantage and a disadvantage for organisms. On the advantage side, compartments separate The human body is a complex compartment separated from biochemical processes that might otherwise confl ict with one the outside world by layers of cells. Anatomically, the body is another. For example, protein synthesis takes place in one sub- divided into three major body cavities: the cranial cavity (com- cellular compartment while protein degradation is taking place monly referred to as the skull ), the thoracic cavity (also called the in another. Barriers between compartments, whether inside a thorax ), and the abdominopelvic cavity ( Fig. 3.1 a). Th e cavities cell or inside a body, allow the contents of one compartment to are separated from one another by bones and tissues, and they diff er from the contents of adjacent compartments. An extreme are lined with tissue membranes . The cranial cavity { cranium, skull} contains the brain, our primary control center. The thoracic cavity is bounded RUNNING PROBLEM by the spine and ribs on top and sides, with the muscular diaphragm forming the floor. The thorax contains the heart, Pap Tests Save Lives which is enclosed in a membranous pericardial sac {peri -, around + cardium , heart}, and the two lungs, enclosed in sepa- Dr. George Papanicolaou has saved the lives of millions of rate pleural sacs . women by popularizing the Pap test, a screening method that detects the early signs of cervical cancer. In the past 50 Th e abdomen and pelvis form one continuous cavity, the years, deaths from cervical cancer have dropped dramatically abdominopelvic cavity . A tissue lining called the peritoneum in countries that routinely use the Pap test. In contrast, lines the abdomen and surrounds the organs within it (stomach, cervical cancer is a leading cause of death in regions where intestines, liver, pancreas, gallbladder, and spleen). Th e kidneys Pap test screening is not routine, such as Africa and Central lie outside the abdominal cavity, between the peritoneum and America. If detected early, cervical cancer is one of the the muscles and bones of the back, just above waist level. Th e most treatable forms of cancer. Today, Jan Melton, who pelvis contains reproductive organs, the urinary bladder, and had an abnormal Pap test several months ago, returns to the terminal portion of the large intestine. Dr. Baird, her family physician, for a repeat test. The results may determine whether she should undergo treatment for cervical cancer. The Lumens of Some Organs Are Outside the Body Th e hollow organs, such as heart, lungs, blood vessels, and in- testines, create another set of compartments within the body. Th e interior of any hollow organ is called its lumen {lumin, win- dow}. A lumen may be wholly or partially fi lled with air or fl uid.

67 Fig. 3.1 ESSENTIALS

Levels of Organization: Body Compartments

BODY COMPARTMENTS

(a) ANATOMICAL: The Body Cavities (b) FUNCTIONAL: Body Fluid Compartments

POSTERIOR ANTERIOR

Extracellular fluid (ECF) Cells (intracellular Cranial cavity lies outside the cells. fluid, ICF)

Blood Interstitial plasma fluid Fat cell: is the surrounds 50–150 μm extracellular most cells. fluid inside blood vessels. Pleural Ovum: μ sac 100 m Thoracic Pericardial cavity sac Red blood cell: 7.5 μm Diaphragm

Abdominal White blood cavity cell: 15 μm Abdominopelvic cavity Smooth muscle Pelvic cell: 15–200 μm long cavity

Cells subdivide into intracellular compartments (see Fig. 3.4).

(c) Compartments Are Separated by Membranes

Pericardial Tissue membranes Phospholipid bilayers membrane have many cells. create cell membranes.

Cell

Heart Loose connective tissue

The pericardial sac is Seen magnified, the pericardial Each cell of the The cell membrane a tissue that surrounds membrane is a layer of flattened pericardial membrane is a phospholipid the heart. cells supported by connective has a cell membrane bilayer. tissue. surrounding it.

68 Compartmentation: Cells and Tissues

For example, the lumens of blood vessels are fi lled with the fl uid Biological Membranes we call blood. For some organs, the lumen is essentially an extension Th e word membrane {membrana, a skin} has two meanings in bi- of the external environment, and material in the lumen is not ology. Before the invention of microscopes in the sixteenth cen- truly part of the body’s internal environment until it crosses tury, a membrane always described a tissue that lined a cavity or the wall of the organ. For example, we think of our digestive separated two compartments. Even today, we speak of mucous tract as being “inside” our body, but in reality its lumen is part membranes in the mouth and vagina, the peritoneal membrane of the body’s external environment . An analogy would be the that lines the inside of the abdomen, the pleural membrane that hole through a bead. Th e hole passes through the bead but is not covers the surface of the lungs, and the pericardial membrane actually inside the bead. that surrounds the heart. Th ese visible membranes are tissues: An interesting illustration of this distinction between the thin, translucent layers of cells. internal environment and the external environment in a lumen Once scientists observed cells with a microscope, the na- 3 involves the bacterium Escherichia coli. Th is organism normally ture of the barrier between a cell’s intracellular fl uid and its ex- lives and reproduces inside the large intestine, an internalized ternal environment became a matter of great interest. By the compartment whose lumen is continuous with the external en- 1890s, scientists had concluded that the outer surface of cells, vironment. When E. coli is residing in this location, it does not the cell membrane, was a thin layer of lipids that separated harm the host. However, if the intestinal wall is punctured by the aqueous fl uids of the interior and outside environment. We disease or accident and E. coli enters the body’s internal envi- now know that cell membranes consist of microscopic double ronment, a serious infection can result. layers ( bilayers ) of phospholipids with protein molecules in- serted in them. Th us, the word membrane may apply either to a tissue or to Functionally, the Body Has a phospholipid-protein boundary layer (Fig. 3.1 c). To add to the Three Fluid Compartments confusion, tissue membranes are oft en depicted in book illustra- tions as a single line, leading students to think of them as if they In physiology we are oft en more interested in functional com- were similar in structure to the cell membrane. In this section partments than in anatomical compartments. Most cells of the you will learn more about these phospholipid membranes that body are not in direct contact with the outside world. Instead their create compartments for cells. external environment is the extracellular fl uid. If we think of all the cells of the body together as one unit, we can then divide the body into two main fl uid compartments: (1) the extracellular The Cell Membrane Separates fl uid (ECF) outside the cells and (2) the intracellular fl uid (ICF) within the cells ( Fig. 3.1 b). The extracellular fluid subdivides Cell from Environment further into plasma , the fl uid portion of the blood, and intersti- There are two synonyms for the term cell membrane: plasma tial fl uid { inter -, between + stare, to stand}, which surrounds membrane and plasmalemma. We will use the term cell mem- most cells of the body. Th e dividing wall between ECF and ICF brane in this course rather than plasma membrane or plasma- is the cell membrane. lemma to avoid confusion with the term blood plasma . The general functions of the cell membrane include: 1 Physical isolation. Th e cell membrane is a physical barrier that separates intracellular fluid inside the cell from the RUNNING PROBLEM surrounding extracellular fl uid. 2 Regulation of exchange with the environment. Th e cell Cancer is a condition in which a small group of cells starts to membrane controls the entry of ions and nutrients into the divide uncontrollably and fails to diff erentiate into specialized cell types. Cancerous cells that originate in one tissue can cell, the elimination of cellular wastes, and the release of escape from that tissue and spread to other organs through products from the cell. the circulatory system and the lymph vessels, a process 3 Communication between the cell and its environment. known as metastasis . Th e cell membrane contains proteins that enable the cell to recognize and respond to molecules or to changes in its Q1: Why does the treatment of cancer focus on killing the external environment. Any alteration in the cell membrane cancerous cells? may aff ect the cell’s activities. 4 Structural support. Proteins in the cell membrane hold the cytoskeleton, the cell’s interior structural scaff olding, in place to maintain cell shape. Membrane proteins also cre- ate specialized junctions between adjacent cells or between

69 Compartmentation: Cells and Tissues

cells and the extracellular matrix {extra-, outside}, which is and G. L. Nicolson in 1972 proposed the fl uid mosaic model extracellular material that is synthesized and secreted by of the membrane. Figure 3.2 highlights the major features of the cells. (Secretion is the process by which a cell releases this contemporary model of membrane structure. a substance into the extracellular space.) Cell-cell and cell- Th e lipids of biological membranes are mostly phospholip- matrix junctions stabilize the structure of tissues. ids arranged in a bilayer so that the phosphate heads are on the membrane surfaces and the lipid tails are hidden in the center How can the cell membrane carry out such diverse func- of the membrane ( Fig. 3.2 b). Th e cell membrane is studded with tions? Th e answer lies in our current model of cell membrane protein molecules, like raisins in a slice of bread, and the extra- structure. cellular surface has glycoproteins and glycolipids. All cell mem- branes are of relatively uniform thickness, about 8 nm. Membranes Are Mostly Lipid and Protein In the early decades of the twentieth century, researchers trying to decipher membrane structure ground up cells and analyzed their Membrane Lipids Create a Hydrophobic Barrier composition. Th ey discovered that all biological membranes con- Th ree main types of lipids make up the cell membrane: phospho- sist of a combination of lipids and proteins plus a small amount of lipids, sphingolipids, and cholesterol. Phospholipids are made of carbohydrate. However, a simple and uniform structure did not a glycerol backbone with two fatty acid chains extending to one account for the highly variable properties of membranes found in side and a phosphate group extending to the other. Th e glycerol- diff erent types of cells. How could water cross the cell membrane phosphate head of the molecule is polar and thus hydrophilic. to enter a red blood cell but not be able to enter certain cells of Th e fatty acid “tail” is nonpolar and thus hydrophobic. the kidney tubule? Th e explanation had to lie in the molecular ar- When placed in an aqueous solution, phospholipids orient rangement of the proteins and lipids in the various membranes. themselves so that the polar heads of the molecules interact with Th e ratio of protein to lipid varies widely, depending on the the water molecules while the nonpolar fatty acid tails “hide” source of the membrane ( Tbl. 3.1 ). Generally, the more meta- by putting the polar heads between themselves and the water. bolically active a membrane is, the more proteins it contains. For Th is arrangement can be seen in three structures: the micelle, example, the inner membrane of a mitochondrion, which con- the liposome, and the phospholipid bilayer of the cell mem- tains enzymes for ATP production, is three-quarters protein. brane ( Fig. 3.2 a). Micelles are small droplets with a single layer Th is chemical analysis of membranes was useful, but it did of phospholipids arranged so that the interior of the micelle is not explain the structural arrangement of lipids and proteins fi lled with hydrophobic fatty acid tails. Micelles are important in in a membrane. Studies in the 1920s suggested that there was the digestion and absorption of fats in the digestive tract. enough lipid in a given area of membrane to create a double Liposomes are larger spheres with bilayer phospholipid layer. Th e bilayer model was further modifi ed in the 1930s to walls. Th is arrangement leaves a hollow center with an aqueous account for the presence of proteins. With the introduction of core that can be fi lled with water-soluble molecules. Biologists electron microscopy, scientists saw the cell membrane for the think that a liposome-like structure was the precursor of the fi rst time. Th e 1960s model of the membrane, as seen in in elec- fi rst living cell. Today, liposomes are being used as a medium to tron micrographs, was a “butter sandwich”—a clear layer of lip- deliver drugs and cosmetics through the skin. ids sandwiched between two dark layers of protein. Phospholipids are the major lipid of membranes, but some By the early 1970s, freeze-fracture electron micrographs membranes also have significant amounts of sphingolipids. had revealed the actual three-dimensional arrangement of lipids Sphingolipids also have fatty acid tails, but their heads may be and proteins within cell membranes. Because of what scientists either phospholipids or glycolipids. Sphingolipids are slightly learned from looking at freeze-fractured membranes, S. J. Singer longer than phospholipids.

Table Composition of Selected Membranes 3.1

Membrane Protein Lipid Carbohydrate

Red blood cell membrane 49% 43% 8%

Myelin membrane around nerve cells 18% 79% 3%

Inner mitochondrial membrane 76% 24% 0%

70 (a) Membrane Phospholipids

Membrane phospholipids form bilayers, micelles, Polar head (hydrophilic) or liposomes. They arrange themselves so that Stylized their nonpolar tails are not in contact with model Nonpolar fatty acid tail aqueous solutions such as extracellular fluid. (hydrophobic)

can arrange themselves as

Phospholipid bilayer Micelles are droplets of phospholipids. Liposomes have forms a sheet. They are important in lipid digestion. an aqueous center.

(b) The Fluid Mosaic Model of Biological Membranes

Peripheral proteins can Glycoprotein be removed without disrupting the integrity of the membrane. This membrane- Transmembrane spanning protein proteins cross the crosses the membrane lipid bilayer. seven times.

Carbohydrate Extracellular fluid Phospholipid heads face COOH the aqueous intracellular and extracellular compartments.

Lipid-anchored proteins Peripheral Lipid tails form protein the interior Cytoplasm Cytoskeleton layer of the proteins membrane. Phosphate Intracellular fluid Cholesterol molecules insert Cell NH2 Cytoplasmic themselves into the lipid layer. membrane loop

(c) Concept Map of Cell Membrane Components Cell Membrane

consists of

Cholesterol Phospholipids, Sphingolipids Carbohydrates Proteins

together form together form together form

Lipid bilayer Glycolipids Glycoproteins

functions as whose functions include Selective barrier between cytosol and external environment Structural stability Cell recognition Immune response

71 Compartmentation: Cells and Tissues

fl uid. Carbohydrates may attach to the extracellular loops, and BIOTECHNOLOGY phosphate groups may attach to the intracellular loops. Phos- phorylation of proteins is one regulatory method cells use to al- ter protein function . Liposomes for Beauty and Health Transmembrane proteins are classified into families ac- Many people fi rst hear the term liposome in connection cording to how many transmembrane segments they have. with cosmetic skin creams that promise to deliver ingre- Many physiologically important membrane proteins have seven dients to the cells that need them. This is not the only use transmembrane segments, as shown in Figure 3.2 c. Others cross for these tiny structures, however. Cosmetic manufacturers the membrane only once or up to as many as 12 times. have simply adopted a medical technique developed to Membrane-spanning proteins are integral proteins, tightly enhance the delivery of drugs. In medicine, the centers of but not covalently bound to the membrane. Th e 20–25 amino liposomes are fi lled with drugs or with fragments of DNA for acids in the protein chain segments that pass through the bilayer gene therapy. Then the liposomes are applied to the skin or are nonpolar. This allows those amino acids to create strong injected into the bloodstream. To make drug delivery more specifi c, researchers now can make immunoliposomes that noncovalent interactions with the lipid tails of the membrane use antibodies to recognize specifi c types of cancer cells. By phospholipids, holding them tightly in place. targeting the drugs to the cells they are treating, research- Some membrane proteins that were previously thought to ers hope to increase the eff ectiveness of the drugs and de- be peripheral proteins are now known to be lipid-anchored pro- crease unwanted side eff ects. To learn more about this topic, teins (Fig. 3.2 b). Some of these proteins are covalently bound to Google liposome drug delivery or immunoliposomes . lipid tails that insert themselves into the bilayer. Others, found only on the external surface of the cell, are held by a GPI an- chor that consists of a membrane lipid plus a sugar-phosphate chain. (GPI stands for glycosylphosphatidylinositol. ) Many lipid- Cholesterol is also a significant part of many cell mem- anchored proteins are found in association with membrane branes. Cholesterol molecules, which are mostly hydrophobic, sphingolipids, leading to the formation of specialized patches insert themselves between the hydrophilic heads of phospholip- of membrane called lipid raft s ( Fig. 3.3 ). Th e longer tails of ids ( Fig. 3.2 b). Cholesterol helps make membranes impermeable the sphingolipids elevate the lipid raft s over their phospholipid to small water-soluble molecules and keeps membranes fl exible neighbors. over a wide range of temperatures.

Membrane Proteins May Be Loosely or Tightly Bound to the Membrane According to some estimates, membrane proteins may be nearly one-third of all proteins coded in our DNA. Each cell has be- tween 10 and 50 different types of proteins inserted into its membranes. Membrane proteins can be described several diff er- ent ways. Integral proteins are tightly bound to the membrane, and the only way they can be removed is by disrupting the membrane structure with detergents or other harsh methods that destroy the membrane’s integrity. Integral proteins include transmembrane proteins and lipid-anchored proteins. Peripheral proteins {peripheria, circumference} are attached to other membrane proteins by noncovalent interac- tions and can be separated from the membrane by chemical methods that do not disrupt the integrity of the membrane. Pe- ripheral proteins include enzymes and some structural binding Fig. 3.3 Lipid rafts are made of sphingolipids. Sphingolipids proteins that anchor the cytoskeleton (the cell’s internal “skele- (orange) are longer than phospholipids and stick up above the ton”) to the membrane ( Fig. 3.2 b). phospholipids of the membrane (black). A lipid-anchored enzyme, Transmembrane proteins { trans- across} are also called placental alkaline phosphatase (yellow), is almost always associated membrane-spanning proteins because the protein’s chains extend with a lipid raft. Image courtesy of D. E. Saslowsky, J. Lawrence, X. Ren, all the way across the cell membrane ( Fig. 3.2c ). When a pro- D. A. Brown, R. M. Henderson, and J. M. Edwardson. Placental alkaline tein crosses the membrane more than once, loops of the amino phosphatase is effi ciently targeted to rafts in supported lipid bilayers. acid chain protrude into the cytoplasm and the extracellular J. Biol. Chem. 277: 26966–26970, 2002.

72 Compartmentation: Cells and Tissues

According to the original fluid mosaic model of the cell the fi nal shape and size of a cell and its contents refl ect its func- membrane, membrane proteins could move laterally from tion. Figure 3.1 b shows some of the diff erent cells in the human location to location, directed by protein fi bers that run just un- body. Although these mature cells look very diff erent from one der the membrane surface. However, researchers have learned another, they all started out alike in the early embryo, and they that this is not true of all membrane proteins. Some integral retain many features in common. proteins are anchored to cytoskeleton proteins (Fig. 3.2 b) and are therefore immobile. Th e ability of the cytoskeleton to restrict the movement of integral proteins allows cells to develop polar- Cells Are Divided into Compartments ity, in which different faces of the cell have different proteins Th e structural organization of a cell can be compared to that of and therefore diff erent properties. Th is is particularly important a medieval walled city. Th e city is separated from the surround- in the cells of the transporting epithelia, as you will see in mul- ing countryside by a high wall, with entry and exit strictly con- tiple tissues in the body. trolled through gates that can be opened and closed. Th e city 3 inside the walls is divided into streets and a diverse collection of Membrane Carbohydrates Attach to Both houses and shops with varied functions. Within the city, a ruler Lipids and Proteins in the castle oversees the everyday comings and goings of the city’s inhabitants. Because the city depends on food and raw ma- Most membrane carbohydrates are sugars attached either to terial from outside the walls, the ruler negotiates with the farm- membrane proteins (glycoproteins) or to membrane lipids (gly- ers in the countryside. Foreign invaders are always a threat, so colipids). They are found exclusively on the external surface the city ruler communicates and cooperates with the rulers of of the cell, where they form a protective layer known as the neighboring cities. glycocalyx { glyco-, sweet + kalyx, husk or pod}. Glycoproteins In the cell, the outer boundary is the cell membrane. Like on the cell surface play a key role in the body’s immune re- the city wall, it controls the movement of material between the sponse. For example, the ABO blood groups are determined by cell interior and the outside by opening and closing “gates” made the number and composition of sugars attached to membrane of protein. Th e inside of the cell is divided into compartments sphingolipids. rather than into shops and houses. Each of these compartments Figure 3.2 c is a summary map organizing the structure of has a specifi c purpose that contributes to the function of the cell the cell membrane. as a whole. In the cell, DNA in the nucleus is the “ruler in the castle,” controlling both the internal workings of the cell and its interaction with other cells. Like the city, the cell depends on Concept Check Answers: End of Chapter supplies from its external environment. It must also communi- 1 . Name three types of lipids found in cell membranes. cate and cooperate with other cells to keep the body functioning in a coordinated fashion. 2 . Describe three types of membrane proteins and how they are associated with the cell membrane. Figure 3.4 a is an overview map of cell structure. The cells of the body are surrounded by the dilute salt solution of 3 . Why do phospholipids in cell membranes form a bilayer instead of a the extracellular fl uid. Th e cell membrane separates the inside single layer? environment of the cell (the intracellular fl uid) from the extra- 4 . How many phospholipid bilayers will a substance cross passing into cellular fl uid. a cell? Internally the cell is divided into the cytoplasm and the nucleus . Th e cytoplasm consists of a fl uid portion, called cytosol ; insoluble particles called inclusions; insoluble protein fi bers; and Intracellular Compartments membrane-bound structures collectively known as organelles . Figure 3.4 shows a typical cell from the lining of the small intes- Much of what we know about cells comes from studies of simple tine. It has most of the structures found in animal cells. organisms that consist of one cell. But humans are much more complex, with trillions of cells in their bodies. It has been esti- mated that there are more than 200 diff erent types of cells in the The Cytoplasm Includes Cytosol, Inclusions, human body, each cell type with its own characteristic structure Fibers, and Organelles and function. Th e cytoplasm includes all material inside the cell membrane During development, cells specialize and take specific except for the nucleus. Th e cytoplasm has four components: shapes and functions. Each cell in the body inherits identical genetic information in its DNA, but no one cell uses all this 1 Cytosol { cyto-, c e l l + sol(uble)}, or intracellular fl uid: Th e information. During diff erentiation, only selected genes acti- cytosol is a semi-gelatinous fl uid separated from the extra- vate, transforming the cell into a specialized unit. In most cases, cellular fl uid by the cell membrane. Th e cytosol contains

73 Fig. 3.4 REVIEW

Cell Structure (a) This is an overview map of cell structure. The cell membrane separates the inside (b) Cytoskeleton environment of the cell (the intracellular fluid) from the extracellular fluid. Internally the cell is divided into the cytoplasm and the Microvilli increase cell nucleus. The cytoplasm consists of a fluid surface area. They are portion, called the cytosol; membrane- supported by microfilaments. bound structures called organelles; insoluble Microfilaments form a network particles called inclusions; and protein fibers just inside the cell membrane. that create the cytoskeleton. Microtubules are the largest cytoskeleton fiber.

THE CELL Intermediate filaments include myosin and keratin. is composed of

Cell membrane

Nucleus Cytoplasm

Membranous Cytosol organelles Inclusions Protein fibers

t
.JUPDIPOESJB t
-JQJE
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'MBHFMMB apparatus t
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Extracellular fluid

(c) Peroxisomes (d) Lysosomes (e) Centrioles

Peroxisomes contain enzymes Lysosomes are small, spherical Centrioles are made from that break down fatty acids and storage vesicles that contain microtubules and direct DNA some foreign materials. powerful digestive enzymes. movement during cell division.

Centrioles

74 (f) Cell Membrane

The cell membrane is a phospholipid bilayer studded with proteins that act as TUSVDUVSBM
BODIPST
USBOTQPSUFST
FO[ZNFT
PS
TJHOBM
SFDFQUPST
(MZDPMJQJET
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glycoproteins occur only on the extracellular surface of the membrane. The cell membrane acts as both a gateway and a barrier between the cytoplasm and the extracellular fluid.

(g) Mitochondria

Outer membrane Mitchondria are spherical to elliptical organelles with a double wall that creates two Intermembrane space separate compartments within the organelle. The inner matrix is surrounded by a membrane that folds into leaflets calledcristae . The intermembrane space, which Cristae MJFT
CFUXFFO
UIF
UXP
NFNCSBOFT
QMBZT
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QSPEVDUJPO
Matrix .JUPDIPOESJB
BSF
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(h) Golgi Apparatus

The Golgi apparatus consists of a series of hollow curved sacs called cisternae Vesicle TUBDLFE
PO
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BOPUIFS
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TVSSPVOEFE
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Cisternae participates in protein modification and packaging.

(i) Endoplasmic Reticulum (ER)

Rough ER The endoplasmic reticulum (ER) is a network of interconnected membrane tubes that are a continuation of the outer nuclear membrane. Rough endoplasmic reticu- Ribosomes lum has a granular appearance due to rows of ribosomes dotting its cytoplasmic surface. Smooth endoplasmic reticulum lacks ribosomes and appears as smooth membrane tubes. The rough ER is the main site of protein synthesis. The smooth ER synthesizes lipids and, in some cells, concentrates and stores calcium ions. Smooth ER

(j) Nucleus

The nucleus is surrounded by a double-membrane nuclear envelope. Both mem- Nuclear branes of the envelope are pierced here and there by pores to allow communication envelope with the cytoplasm. The outer membrane of the nuclear envelope connects to the endoplasmic reticulum membrane. In cells that are not dividing, the nucleus appears filled with randomly scattered granular material composed of DNA and proteins. Nucleolus Usually a nucleus also contains from one to four larger dark-staining bodies of DNA, RNA, and protein called nucleoli.

Nuclear pores

75 Compartmentation: Cells and Tissues

RUNNING PROBLEM Inclusions Are in Direct Contact with the Cytosol The inclusions of cells do not have boundary membranes and During a Pap test for cervical cancer, tissue is sampled from so are in direct contact with the cytosol. Movement of material the cervix (neck) of the uterus with a collection device that resembles a tiny brush. The cells are rinsed off the brush between inclusions and the cytosol does not require transport into preservative fl uid that is sent to a laboratory. There the across a membrane. Nutrients are stored as glycogen granules sample is processed onto a glass slide that will be examined and lipid droplets. Most inclusions with functions other than fi rst by a computer, then by a trained cytologist. The nutrient storage are made from protein or combinations of RNA computer and cytologist look for dysplasia { dys-, abnormal + and protein. - plasia , growth or cell multiplication}, a change in the size and Ribosomes ( Fig. 3.4 i) are small, dense granules of RNA shape of cells that is suggestive of cancerous changes. Cancer and protein that manufacture proteins under the direction of cells can usually be recognized by a large nucleus surrounded the cell’s DNA. Ribosomes attached to the cytosolic surface of by a relatively small amount of cytoplasm. Jan’s fi rst Pap test organelles are called fi xed ribosomes. Th ose suspended free showed all the hallmarks of dysplasia. in the cytosol are free ribosomes. Some free ribosomes form Q2: What is happening in cancer cells that explains the large groups of 10 to 20 known as polyribosomes. A ribosome that size of their nucleus and the relatively small amount of is fi xed one minute may release and become a free ribosome cytoplasm? the next. Ribosomes are most numerous in cells that synthe- size proteins for export out of the cell.

Cytoplasmic Protein Fibers Come dissolved nutrients and proteins, ions, and waste products. in Three Sizes The other components of the cytoplasm—inclusions, fi- The three families of cytoplasmic protein fibers are classified bers, and organelles—are suspended in the cytosol. by diameter and protein composition ( Tbl. 3.2 ). All fi bers are 2 Inclusions are particles of insoluble materials. Some are polymers of smaller proteins. Th e thinnest are actin fi bers, also stored nutrients. Others are responsible for specific cell called microfi laments . Somewhat larger intermediate fi laments functions. Th ese structures are sometimes called the non- may be made of different types of protein, including keratin membranous organelles . in hair and skin, and neurofi lament in nerve cells. Th e largest 3 Insoluble protein fibers form the cell’s internal support protein fi bers are the hollow microtubules, made of a protein system, or cytoskeleton . called tubulin. A large number of accessory proteins are associ- 4 Organelles —“little organs”—are membrane-bounded ated with the cell’s protein fi bers. compartments that play specifi c roles in the overall func- The insoluble protein fibers of the cell have two general tion of the cell. For example, the organelles called mito- purposes: structural support and movement. Structural support chondria (singular, mitochondrion) generate most of the comes primarily from the cytoskeleton. Movement of the cell or cell’s ATP, and the organelles called lysosomes act as the of elements within the cell takes place with the aid of protein digestive system of the cell. Th e organelles work in an in- fi bers and a group of specialized enzymes called motor proteins. tegrated manner, each organelle taking on one or more of Th ese functions are discussed in more detail in the sections that the cell’s functions. follow.

Table Diameter of Protein Fibers in the Cytoplasm 3.2

Diameter Type of Protein Functions

Microfilaments 7 nm Actin (globular) Cytoskeleton; associates with myosin for muscle contraction

Intermediate 10 nm Keratin, neurofilament Cytoskeleton, hair and nails, protective barrier of skin filaments protein (filaments)

Microtubules 25 nm Tubulin (globular) Movement of cilia, flagella, and chromosomes; intracellular transport of organelles; cytoskeleton

76 Compartmentation: Cells and Tissues

Microtubules Form Centrioles, Cilia, and Flagella The largest cytoplasmic protein fibers, the microtubules, cre- EMERGING CONCEPTS ate the complex structures of centrioles, cilia, and flagella, which are all involved in some form of cell movement. Th e cell’s Single Cilia Are Sensors microtubule-organizing center, the centrosome, assembles tu- Cilia in the body are not limited to the airways and the bulin monomers into microtubules. The centrosome appears female reproductive tract. Scientists have known for years as a region of darkly staining material close to the cell nucleus. that most cells of the body contain a single, stationary, or In most animal cells, the centrosome contains two centrioles, non-motile , cilium, but they thought that these solitary shown in the typical cell of Figure 3.4 e. Each centriole is a cy- primary cilia were mostly evolutionary remnants and lindrical bundle of 27 microtubules, arranged in nine triplets. of little signifi cance. Primary cilia diff er structurally from In cell division, the centrioles direct the movement of DNA motile cilia because they lack the central pair of microtubules 3 strands. Cells that have lost their ability to undergo cell division, found in motile cilia (a 9 + 0 arrangement instead of 9 + 2; such as mature nerve cells, lack centrioles. see Fig. 3.5). Researchers in recent years have learned that Cilia are short, hairlike structures projecting from the cell primary cilia actually serve a function. They can act as sensors of the external environment, passing information surface like the bristles of a brush {singular, cilium, Latin for into the cell. For example, primary cilia in photoreceptors eyelash}. Most cells have a single short cilium, but cells lining of the eye help with light sensing, and primary cilia in the upper airways and part of the female reproductive tract are the kidney sense fl uid fl ow. Using molecular techniques, covered with cilia. In these tissues, ciliary movement, like a wav- scientists have found that these small, insignifi cant hairs ing fi eld of grain, creates currents that sweep fl uids or secretions play critical roles during embryonic development as well. across the cell surface. Mutations to ciliary proteins cause disorders (ciliopathies ) Th e surface of a cilium is a continuation of the cell membrane. ranging from polycystic kidney disease and loss of vision to Th e core of motile, or moving, cilia contains nine pairs of micro- cancer. The role of primary cilia in other disorders, including tubules surrounding a central pair ( Fig. 3.5 b). Th e microtubules obesity, is currently a hot topic in research. terminate just inside the cell at the basal body. These cilia beat rhythmically back and forth when the microtubule pairs in their core slide past each other with the help of the motor protein dynein . Flagella have the same microtubule arrangement as cilia one surface almost totally covered with cilia ( Fig. 3.5 a). The but are considerably longer {singular, fl agellum, Latin for whip}. wavelike movements of the fl agellum push the sperm through Flagella are found on free-fl oating single cells, and in humans fl uid, just as undulating contractions of a snake’s body push it the only fl agellated cell is the male sperm cell. A sperm cell has headfi rst through its environment. Flagella bend and move by only one fl agellum, in contrast to ciliated cells, which may have the same basic mechanism as cilia.

Fluid movement

Flagellum Microtubules

Fluid movement

Cilium

Cell membrane

Cilia

(a) Cilia (b) Cilia and flagella have 9 pairs of (c) The beating of cilia and flagella microtubules surrounding a central pair. creates fluid movement.

Fig. 3.5 Centrioles, cilia, and fl agella. All three structures are formed from microtubules.

77 Compartmentation: Cells and Tissues

The Cytoskeleton Is a Changeable Scaff old dyneins. All three groups use energy stored in ATP to propel themselves along cytoskeleton fi bers. The cytoskeleton is a flexible, changeable three-dimensional Myosins bind to actin fi bers and are best known for their scaff olding of actin microfi laments, intermediate fi laments, and role in muscle contraction. Kinesins and dyneins assist the microtubules that extends throughout the cytoplasm. Some movement of vesicles along microtubules. Dyneins also associ- cytoskeleton protein fi bers are permanent, but most are synthe- ate with the microtubule bundles of cilia and fl agella to help cre- sized or disassembled according to the cell’s needs. Because of ate their whiplike motion. the cytoskeleton’s changeable nature, its organizational details Most motor proteins are made of multiple protein chains are complex and are not discussed in detail here. arranged into three parts: two heads that bind to the cytoskel- Th e cytoskeleton has at least fi ve important functions. eton fi ber, a neck, and a tail region that is able to bind “cargo,” 1 Cell shape. The protein scaffolding of the cytoskeleton such as an organelle that needs to be transported through the provides mechanical strength to the cell and in some cells cytoplasm ( Fig. 3.6 ). Th e heads alternately bind to the cyto- plays an important role in determining the shape of the skeleton fi ber, then release and “step” forward using the energy cell. Figure 3.4 b shows how cytoskeletal fi bers help sup- stored in ATP. port microvilli { micro-, small + villus, tuft of hair}, fi nger- like extensions of the cell membrane that increase the Concept Check Answers: End of Chapter surface area for absorption of materials. 2 Internal organization. C y t o s k e l e t a l fi bers stabilize the po- 5 . Name the three sizes of cytoplasmic protein fi bers. sitions of organelles. Figure 3.4 b illustrates organelles held 6. How would the absence of a fl agellum aff ect a sperm cell? in place by the cytoskeleton. Note, however, that this fi gure is only a snapshot of one moment in the cell’s life. Th e in- 7. What is the diff erence between cytoplasm and cytosol? terior arrangement and composition of a cell are dynamic, 8. What is the diff erence between a cilium and a fl agellum? changing from minute to minute in response to the needs 9. What is the function of motor proteins? of the cell, just as the inside of the walled city is always in motion. One disadvantage of the static illustrations in text- books is that they are unable to represent movement and the dynamic nature of many physiological processes accurately. Organelles Create Compartments 3 Intracellular transport. Th e cytoskeleton helps transport for Specialized Functions materials into the cell and within the cytoplasm by serv- ing as an intracellular “railroad track” for moving organ- Organelles are subcellular compartments separated from the elles. Th is function is particularly important in cells of the cytosol by one or more phospholipid membranes similar in nervous system, where material must be transported over structure to the cell membrane. The compartments created intracellular distances as long as a meter. 4 Assembly of cells into tissues. Protein fi bers of the cyto- skeleton connect with protein fibers in the extracellular space, linking cells to one another and to supporting mate- Organelle rial outside the cells. In addition to providing mechanical strength to the tissue, these linkages allow the transfer of information from one cell to another. 5 Movement. The cytoskeleton helps cells move. For ex- ample, the cytoskeleton helps white blood cells squeeze Motor out of blood vessels and growing nerve cells send out long protein extensions as they elongate. Cilia and fl agella on the cell ATP membrane are able to move because of their microtubule cytoskeleton. Special motor proteins facilitate movement Direction of and intracellular transport by using energy from ATP to movement slide or step along cytoskeletal fi bers. Motor Proteins Create Movement Cytoskeletal fiber Fig. 3.6 Motor proteins. Motor proteins have multiple protein Motor proteins are proteins that are able to convert stored en- chains that form two heads, a neck, and a tail that can bind to organ- ergy into directed movement. Th ree groups of motor proteins elles or other cargo. The heads “walk” along cytoskeletal fi bers with are associated with the cytoskeleton: myosins, kinesins, and the help of energy from ATP.

78 Compartmentation: Cells and Tissues by organelles allow the cell to isolate substances and segregate endoplasmic reticulum : rough endoplasmic reticulum (RER) functions. For example, an organelle might contain substances and smooth endoplasmic reticulum (SER). that could be harmful to the cell, such as digestive enzymes. Th e rough endoplasmic reticulum is the main site of pro- Figures 3.4 g, 3.4 h, and 3.4 i show the four major groups of or- tein synthesis. Proteins are assembled on ribosomes attached to ganelles: mitochondria, the Golgi apparatus, the endoplas- the cytoplasmic surface of the rough ER, then inserted into the mic reticulum, and membrane-bound spheres called vesicles rough ER lumen, where they undergo chemical modifi cation. { vesicula, bladder}. The smooth endoplasmic reticulum lacks attached ri- bosomes and is the main site for the synthesis of fatty acids, M i t o c h o n d r i a Mitochondria {singular, mitochondrion; mitos, steroids, and lipids . Phospholipids for the cell membrane are thread + chondros, granule} are unique organelles in several ways. produced here, and cholesterol is modified into steroid hor- First, they have an unusual double wall that creates two sepa- mones, such as the sex hormones estrogen and testosterone. rate compartments within the mitochondrion ( Fig. 3.4 g). In the Th e smooth ER of liver and kidney cells detoxifi es or inactivates 3 center, inside the inner membrane, is a compartment called the drugs. In skeletal muscle cells, a modifi ed form of smooth ER mitochondrial matrix { matrix, female animal for breeding}. stores calcium ions (Ca2+) to be used in muscle contraction. The matrix contains enzymes, ribosomes, granules, and sur- prisingly, its own unique DNA. Th is mitochondrial DNA has Th e Golgi Apparatus Th e Golgi apparatus (also known as the a diff erent nucleotide sequence from that found in the nucleus. Golgi complex) was first described by Camillo Golgi in 1898 Because mitochondria have their own DNA, they can manufac- (Fig. 3.4 h) . For years, some investigators thought that this or- ture some of their own proteins. ganelle was just a result of the fi xation process needed to pre- Why do mitochondria contain DNA when other organelles pare tissues for viewing under the light microscope. However, do not? Th is question has been the subject of intense scrutiny. we now know from electron microscope studies that the Golgi According to the prokaryotic endosymbiont theory, mitochon- apparatus is indeed a discrete organelle. It consists of a series of dria are the descendants of bacteria that invaded cells millions hollow curved sacs, called cisternae, stacked on top of one an- of years ago. Th e bacteria developed a mutually benefi cial re- other like a series of hot water bottles and surrounded by ves- lationship with their hosts and soon became an integral part icles. Th e Golgi apparatus receives proteins made on the rough of the host cells. Supporting evidence for this theory is the fact ER, modifi es them, and packages them into the vesicles. that our mitochondrial DNA, RNA, and enzymes are similar to those in bacteria but unlike those in our own cell nuclei. Cytoplasmic Vesicles Membrane-bound cytoplasmic vesicles The second compartment inside a mitochondrion is the are of two kinds: secretory and storage. Secretory vesicles contain intermembrane space, which lies between the outer and inner proteins that will be released from the cell. Th e contents of most mitochondrial membranes. Th is compartment plays an impor- storage vesicles , however, never leave the cytoplasm. tant role in mitochondrial ATP production, and the number Lysosomes { lysis, dissolution + soma, body} are small stor- of mitochondria in a cell is directly related to the cell’s energy age vesicles that appear as membrane-bound granules in the cyto- needs. For example, skeletal muscle cells, which use a lot of en- plasm ( Fig. 3.4 d). Lysosomes act as the digestive system of the cell. ergy, have many more mitochondria than less active cells, such Th ey use powerful enzymes to break down bacteria or old organ- as adipose (fat) cells. elles, such as mitochondria, into their component molecules. Th ose Another unusual characteristic of mitochondria is their molecules that can be reused are reabsorbed into the cytosol, while ability to replicate themselves even when the cell to which they the rest are dumped out of the cell. As many as 50 types of enzymes belong is not undergoing cell division. Th is process is aided by have been identifi ed from lysosomes of diff erent cell types. the mitochondrial DNA, which allows the organelles to direct Because lysosomal enzymes are so powerful, early workers their own duplication. Mitochondrial replication takes place by puzzled over the question of why these enzymes do not normally budding, during which small daughter mitochondria pinch off destroy the cell that contains them. What scientists discovered from an enlarged parent. For instance, exercising muscle cells was that lysosomal enzymes are activated only by very acidic that experience increased energy demands over a period of time conditions, 100 times more acidic than the normal acidity level may meet the demand for more ATP by increasing the number in the cytoplasm. When lysosomes fi rst pinch off from the Golgi of mitochondria in their cytoplasm. apparatus, their interior pH is about the same as that of the cyto- sol, 7.0–7.3. Th e enzymes are inactive at this pH. Th eir inactivity The Endoplasmic Reticulum The endoplasmic reticulum, serves as a form of insurance. If the lysosome breaks or acciden- or ER, is a network of interconnected membrane tubes with tally releases enzymes, they will not harm the cell. three major functions: synthesis, storage, and transport of However, as the lysosome sits in the cytoplasm, it accumu- biomolecules (Fig. 3.4 i). Th e name reticulum comes from the lates H+ in a process that uses energy. Increasing concentrations Latin word for net and refers to the netlike arrangement of the of H+ decrease the pH inside the vesicle to 4.8–5.0, and the en- tubules. Electron micrographs reveal that there are two forms of zymes activate. Once activated, lysosomal enzymes can break

79 Compartmentation: Cells and Tissues

down biomolecules inside the vesicle. Th e lysosomal membrane The Nucleus Is the Cell’s Control Center is not aff ected by the enzymes. The digestive enzymes of lysosomes are not always kept Th e nucleus of the cell contains DNA, the genetic material that isolated within the organelle. Occasionally, lysosomes release ultimately controls all cell processes. Figure 3.4 j illustrates the their enzymes outside the cell to dissolve extracellular support structure of a typical nucleus. Its boundary, or nuclear enve- material, such as the hard calcium carbonate portion of bone. lope, is a two-membrane structure that separates the nucleus In other instances, cells allow their lysosomal enzymes to come from the cytoplasmic compartment. Both membranes of the en- in contact with the cytoplasm, leading to self-digestion of all or velope are pierced here and there by round holes, or pores. part of the cell. When muscles atrophy (shrink) from lack of use Communication between the nucleus and cytosol occurs or the uterus diminishes in size aft er pregnancy, the loss of cell through the nuclear pore complexes, large protein complexes mass is due to the action of lysosomes. with a central channel. Ions and small molecules move freely Th e inappropriate release of lysosomal enzymes has been through this channel when it is open, but transport of large implicated in certain disease states, such as the infl ammation molecules such as proteins and RNA is a process that requires and destruction of joint tissue in rheumatoid arthritis. In the energy. Specifi city of the transport process allows the cell to re- inherited conditions known as lysosomal storage diseases, lyso- strict DNA to the nucleus and various enzymes to either the cy- somes are ineff ective because they lack specifi c enzymes. One of toplasm or the nucleus. the best-known lysosomal storage diseases is the fatal inherited In electron micrographs of cells that are not dividing, condition known as Tay-Sachs disease . Infants with Tay-Sachs the nucleus appears fi lled with randomly scattered granular disease have defective lysosomes that fail to break down glyco- material, or chromatin, composed of DNA and associated lipids. Accumulation of glycolipids in nerve cells causes nervous proteins. Usually a nucleus also contains from one to four system dysfunction, including blindness and loss of coordina- larger dark-staining bodies of DNA, RNA, and protein called tion. Most infants affl icted with Tay-Sachs disease die in early nucleoli {singular, nucleolus, little nucleus}. Nucleoli contain childhood. the genes and proteins that control the synthesis of RNA for Peroxisomes are storage vesicles that are even smaller than ribosomes. lysosomes (Fig. 3.4 c). For years, they were thought to be a kind Th e process of protein synthesis, modifi cation, and pack- of lysosome, but we now know that they contain a diff erent set aging in different parts of the cell is an excellent example of of enzymes. Th eir main function appears to be to degrade long- how compartmentation allows separation of function, as shown chain fatty acids and potentially toxic foreign molecules. in Figure 3.7 . RNA for protein synthesis is made from DNA Peroxisomes get their name from the fact that the reac- templates in the nucleus 1 , then transported to the cytoplasm tions that take place inside them generate hydrogen peroxide through the nuclear pores 2 . In the cytoplasm, proteins are syn- thesized on ribosomes that may be free inclusions 3 or attached ( H 2O2), a toxic molecule. Th e peroxisomes rapidly convert this peroxide to oxygen and water using the enzyme catalase . Per- to the rough endoplasmic reticulum 4 . Th e newly made protein oxisomal disorders disrupt the normal processing of lipids and is compartmentalized in the lumen of the rough ER 5 , where it can severely disrupt neural function by altering the structure is modifi ed before being packaged into a vesicle 6 . Th e vesicles of nerve cell membranes. fuse with the Golgi apparatus, allowing additional modifi cation of the protein in the Golgi lumen 7 . The modified proteins leave the Golgi packaged in either storage vesicles 9 or secre- Concept Check Answers: End of Chapter tory vesicles whose contents will be released into the extracel- lular fl uid 10. 10. What distinguishes organelles from inclusions? 11. What is the anatomical difference between rough endoplasmic reticulum and smooth endoplasmic reticulum? What is the functional Tissues of the Body diff erence? Despite the amazing variety of intracellular structures, no single 12. How do lysosomes diff er from peroxisomes? cell can carry out all the processes of the mature human body. Instead, cells assemble into the larger units we call tissues. Th e 13. Apply the physiological theme of compartmentation to organelles in cells in tissues are held together by specialized connections general and to mitochondria in particular. called cell junctions and by other support structures. Tissues 14. Microscopic examination of a cell reveals many mitochondria. What range in complexity from simple tissues containing only one does this observation imply about the cell’s energy requirements? cell type, such as the lining of blood vessels, to complex tissues 15. Examining tissue from a previously unknown species of fish, you containing many cell types and extensive extracellular material, discover a tissue containing large amounts of smooth endoplasmic such as connective tissue. Th e cells of most tissues work together reticulum in its cells. What is one possible function of these cells? to achieve a common purpose.

80 Compartmentation: Cells and Tissues

Nucleus

Ribosome Peroxisome mRNA Targeted 3 proteins 1 DNA Growing amino-acid 2 chain Mitochondrion

Cytosolic protein 1 mRNA is transcribed from genes in the DNA. 3

4 2 mRNA leaves the nucleus and attaches to cytosolic Nuclear Endoplasmic ribosomes, initiating protein pore synthesis. reticulum 5

3 Some proteins are released by Transport vesicle free ribosomes into the cytosol or are targeted to specific 6 organelles.

4 Ribosomes attached to the rough endoplasmic reticulum Golgi apparatus direct proteins destined for packaging into the lumen of Retrograde the rough ER. Golgi-ER transport 5 Proteins are modified as they pass through the lumen of 7 the ER. Golgi 6 Transport vesicles move the 8 proteins from the ER to the Golgi apparatus.

7 Golgi cisternae migrate toward the cell membrane.

9 8 Some vesicles bud off the Secretory cisternae and move in a Lysosome or vesicle retrograde or backward Golgi storage vesicle apparatus fashion. 10 9 Some vesicles bud off to form lysosomes or storage vesicles.

Cytosol 10 Other vesicles become secretory vesicles that release Cell their contents outside the cell. membrane Extracellular fluid Fig. 3.7 Protein synthesis shows the importance of subcellular compartmentation.

81 Compartmentation: Cells and Tissues

The study of tissue structure and function is known as histology {histos, tissue}. Histologists describe tissues by their Table 3.3 physical features: (1) the shape and size of the cells, (2) the ar- Major Cell Adhesion Molecules (CAMs) rangement of the cells in the tissue (in layers, scattered, and so on), (3) the way cells are connected to one another, and (4) the Name Examples amount of extracellular material present in the tissue. Th ere are four primary tissue types in the human body: epithelial, con- Cadherins Cell-cell junctions such as adherens nective, muscle, and neural, or nerve. Before we consider each junctions and desmosomes. Calcium-dependent. tissue type specifi cally, let’s examine how cells link together to form tissues. Integrins Primarily found in cell-matrix junctions. These also function in cell Extracellular Matrix Has Many Functions signaling. Immunoglobulin NCAMs (nerve-cell adhesion Extracellular matrix (usually just called matrix) is extracellular superfamily CAMs molecules). Responsible for nerve material that is synthesized and secreted by the cells of a tissue. cell growth during nervous system For years, scientists believed that matrix was an inert substance development. whose only function was to hold cells together. However, exper- imental evidence now shows that the extracellular matrix plays a Selectins Temporary cell-cell adhesions. vital role in many physiological processes, ranging from growth and development to cell death. A number of disease states are associated with overproduction or disruption of extracellular molecules, or NCAMs. Cell adhesion helps white blood cells es- matrix, including chronic heart failure and the spread of cancer- cape from the circulation and move into infected tissues, and it ous cells throughout the body ( metastasis ). allows clumps of platelets to cling to damaged blood vessels. Be- Th e composition of extracellular matrix varies from tissue cause cell adhesions are not permanent, the bond between those to tissue, and the mechanical properties, such as elasticity and CAMs and matrix is weak. fl exibility, of a tissue depend on the amount and consistency of Stronger cell junctions can be grouped into three broad the tissue’s matrix. Matrix always has two basic components: categories by function: communicating junctions, occlud- proteoglycans and insoluble protein fi bers. Proteoglycans are ing junctions { occludere, to close up}, and anchoring junctions glycoproteins, which are proteins covalently bound to polysac- ( Fig. 3.8 ). In animals, the communicating junctions are gap charide chains. Insoluble protein fi bers such as collagen , fi bro- junctions. Th e occluding junctions of vertebrates are tight junc- nectin, and laminin provide strength and anchor cells to the tions that limit movement of materials between cells. Animals matrix. Attachments between the extracellular matrix and pro- have three major types of junctions, described below. teins in the cell membrane or the cytoskeleton are ways cells 1 Gap junctions are the simplest cell-cell junctions communication with their external environment. (Fig. 3.8 b). Th ey allow direct and rapid cell-to-cell com- The amount of extracellular matrix in a tissue is highly munication through cytoplasmic bridges between adjoin- variable. Nerve and muscle tissue have very little matrix, but the ing cells. Cylindrical proteins called connexins interlock to connective tissues, such as cartilage, bone, and blood, have ex- create passageways that look like hollow rivets with nar- tensive matrix that occupies as much volume as their cells. Th e row channels through their centers. Th e channels are able consistency of extracellular matrix can vary from watery (blood to open and close, regulating the movement of small mol- and lymph) to rigid (bone). ecules and ions through them. Gap junctions allow both chemical and electrical sig- Cell Junctions Hold Cells Together nals to pass rapidly from one cell to the next. Th ey were once thought to occur only in certain muscle and nerve to Form Tissues cells, but we now know they are important in cell-to-cell During growth and development, cells form cell-cell adhesions communication in many tissues, including the liver, pan- that may be transient or that may develop into more permanent creas, ovary, and thyroid gland. cell junctions. Cell adhesion molecules, or CAMs, are mem- 2 Tight junctions are occluding junctions that restrict brane-spanning proteins responsible both for cell junctions and the movement of material between the cells they link for transient cell adhesions ( Tbl. 3.3 ). Cell-cell or cell-matrix (Fig. 3.8 c). In tight junctions, the cell membranes of ad- adhesions mediated by CAMs are essential for normal growth jacent cells partly fuse together with the help of proteins and development. For example, growing nerve cells creep across called claudins and occludins, thereby making a barrier. As the extracellular matrix with the help of nerve-cell adhesion in many physiological processes, the barrier properties of

82 Fig. 3.8 ESSENTIALS

Cell Junctions

(a) Cell junctions connect one cell CELL JUNCTIONS with another cell (or to surrounding matrix) with Function Communicating Occluding Anchoring membrane- spanning proteins called cell adhe- sion molecules, or Location Cell-cell junctions Cell-matrix junctions CAMs. This map shows the many ways cell junctions can be categorized. Type Gap Tight Adherens Desmosome Focal Hemidesmosome junction junction junction adhesion

Membrane Claudin, Connexin Cadherin Integrin protein occludin

Keratin Cytoskeleton Intermediate Actin Actin Actin (intermediate fiber filaments filaments)

Matrix Fibronectin Laminin protein and other proteins

Cell junctions can be grouped into three Cytosol Claudin categories: (b) Gap and occludin Cadherin junctions which allow Connexin proteins proteins proteins direct cell to cell communication, (c) tight Cell Plaque junctions that block membrane Intercellular glycoproteins movement of material space between cells, and (d) anchoring junctions that Cell Intercellular hold cells to one another Cell Cell membrane Cell Cell space Intermediate 1 2 1 2 and to the extracellular filament matrix. (b) Gap junctions are (c) Tight junctions are (d) A desmosome is a communicating junctions. occluding junctions. cell-to-cell anchoring junction.

Heart muscle has gap (e) Cells may have several junctions that allow types of junctions, as chemical and electrical shown in this micro- signals to pass rapidly graph of two adjacent from one cell to the next. Tight junctions intestinal cells. prevent Clusters of gap movement junctions between cells. Adherens junction

Desmosomes anchor cells to each other.

Freeze fracture of cell membrane

83 Compartmentation: Cells and Tissues

tight junctions are dynamic and can be altered depending There are also two types of cell-matrix anchoring junc- on the body’s needs. Tight junctions may have varying de- tions. Hemidesmosomes { hemi-, half} are strong junctions that grees of “leakiness.” anchor intermediate fi bers of the cytoskeleton to fi brous matrix Tight junctions in the intestinal tract and kidney proteins such as laminin. Focal adhesions tie intracellular actin prevent most substances from moving freely between fi bers to diff erent matrix proteins, such as fi bronectin. the external and internal environments. In this way, Th e loss of normal cell junctions plays a role in a number they enable cells to regulate what enters and leaves the of diseases and in metastasis. Diseases in which cell junctions body. Tight junctions also create the so-called blood- are destroyed or fail to form can have disfi guring and painful brain barrier that prevents many potentially harmful symptoms, such as blistering skin. One such disease is pemphi- substances in the blood from reaching the extracellular gus, a condition in which the body attacks some of its own cell fluid of the brain. junction proteins ( www.pemphigus.org ). 3 Anchoring junctions (Fig. 3.8 d) attach cells to each other Th e disappearance of anchoring junctions probably con- (cell-cell anchoring junctions) or to the extracellular ma- tributes to the metastasis of cancer cells throughout the body. trix (cell-matrix anchoring junctions). In vertebrates, Cancer cells lose their anchoring junctions because they have cell-cell anchoring junctions are created by CAMs called fewer cadherin molecules and are not bound as tightly to neigh- cadherins, which connect with one another across the in- boring cells. Once a cancer cell is released from its moorings, tercellular space. Cell-matrix junctions use CAMs called it secretes protein-digesting enzymes known as proteases . Th ese integrins. Integrins are membrane proteins that can also enzymes, especially those called matrix metalloproteinases bind to signal molecules in the cell’s environment, trans- (MMPs), dissolve the extracellular matrix so that escaping can- ferring information carried by the signal across the cell cer cells can invade adjacent tissues or enter the bloodstream. membrane into the cytoplasm. Researchers are investigating ways of blocking MMP enzymes to see if they can prevent metastasis. Anchoring junctions contribute to the mechanical strength Now that you understand how cells are held together into of the tissue. They have been compared to buttons or zippers tissues, we will look at the four diff erent tissue types in the body: that tie cells together and hold them in position within a tissue. (1) epithelial, (2) connective, (3) muscle, and (4) neural. Notice how the interlocking cadherin proteins in Figure 3.8 c re- semble the teeth of a zipper. The protein linkage of anchoring cell junctions is very Concept Check Answers: End of Chapter strong, allowing sheets of tissue in skin and lining body cavities to resist damage from stretching and twisting. Even the tough 16. Name the three functional categories of cell junctions. protein fi bers of anchoring junctions can be broken, however. 17. Which type of cell junction: If you have shoes that rub against your skin, the stress can shear (a) restricts movement of materials between cells? the proteins connecting the diff erent skin layers. When fl uid ac- (b) allows direct movement of substances from the cytoplasm of one cumulates in the resulting space and the layers separate, a blister cell to the cytoplasm of an adjacent cell? results. (c) provides the strongest cell-cell junction? Tissues held together with anchoring junctions are like a (d) anchors actin fi bers in the cell to the extracellular matrix? picket fence, where spaces between the connecting bars allow materials to pass from one side of the fence to the other. Move- ment of materials between cells is known as the paracellular Epithelia Provide Protection and pathway. In contrast, tissues held together with tight junctions are more like a solid brick wall: very little can pass from one side Regulate Exchange of the wall to the other between the bricks. Th e epithelial tissues, or epithelia { epi- , upon + thele -, nipple; Cell-cell anchoring junctions take the form of either adhe- singular epithelium}, protect the internal environment of the rens junctions or desmosomes. Adherens junctions link actin body and regulate the exchange of materials between the inter- fi bers in adjacent cells together, as shown in the micrograph in nal and external environments ( Fig. 3.9 ). Th ese tissues cover Figure 3.8 e. Desmosomes {desmos, b a n d + soma, body} attach exposed surfaces, such as the skin, and line internal passageways, to intermediate fi laments of the cytoskeleton. Desmosomes are such as the digestive tract. Any substance that enters or leaves the the strongest cell-cell junctions. In electron micrographs they internal environment of the body must cross an epithelium . can be recognized by the dense glycoprotein bodies, or plaques, Some epithelia, such as those of the skin and mucous mem- that lie just inside the cell membranes in the region where the branes of the mouth, act as a barrier to keep water in the body two cells connect ( Fig. 3.8e). Desmosomes may be small points and invaders such as bacteria out. Other epithelia, such as those of contact between two cells (spot desmosomes) or bands that in the kidney and intestinal tract, control the movement of ma- encircle the entire cell (belt desmosomes). terials between the external environment and the extracellular

84 Fig. 3.9 ESSENTIALS

Epithelial Tissue

(a) Five Functional Categories of Epithelia

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85 Compartmentation: Cells and Tissues

fl uid of the body. Nutrients, gases, and wastes oft en must cross There are five functional types of epithelia: exchange, several diff erent epithelia in their passage between cells and the transporting, ciliated, protective, and secretory ( Fig. 3.10 ). outside world. Exchange epithelia permit rapid exchange of materials, espe- Another type of epithelium is specialized to manufacture cially gases. Transporting epithelia are selective about what can and secrete chemicals into the blood or into the external envi- cross them and are found primarily in the intestinal tract and ronment. Sweat and saliva are examples of substances secreted the kidney. Ciliated epithelia are located primarily in the airways by epithelia into the environment. Hormones are secreted into of the respiratory system and in the female reproductive tract. the blood. Protective epithelia are found on the surface of the body and just inside the openings of body cavities. Secretory epithelia synthe- Structure of Epithelia Epithelia typically consist of one or size and release secretory products into the external environ- more layers of cells connected to one another, with a thin layer ment or into the blood. of extracellular matrix lying between the epithelial cells and Figure 3.9 b shows the distribution of these epithelia in the their underlying tissues (Fig. 3.9 c). Th is matrix layer, called the systems of the body. Notice that most epithelia face the external basal lamina {bassus, l o w ; lamina, a thin plate}, or basement environment on one surface and the extracellular fl uid on the membrane, is composed of a network of collagen and laminin other. Th e only exception is the endocrine glands. filaments embedded in proteoglycans. The protein filaments hold the epithelial cells to the underlying cell layers, just as Exchange Epithelia Th e exchange epithelia are composed of cell junctions hold the individual cells in the epithelium to one very thin, fl attened cells that allow gases ( CO2 a n d O 2 ) t o p a s s another. rapidly across the epithelium. Th is type of epithelium lines the Th e cell junctions in epithelia are variable. Physiologists blood vessels and the lungs, the two major sites of gas exchange classify epithelia either as “leaky” or “tight,” depending on how in the body. In capillaries, gaps or pores in the epithelium also easily substances pass from one side of the epithelial layer to the allow molecules smaller than proteins to pass between two adja- other. In a leaky epithelium, anchoring junctions allow mol- cent epithelial cells, making this a leaky epithelium (Fig. 3.10 a) . ecules to cross the epithelium by passing through the gap be- Histologists classify thin exchange tissue as simple squamous tween two adjacent epithelial cells. A typical leaky epithelium epithelium because it is a single layer of thin, fl attened cells. Th e is the wall of capillaries (the smallest blood vessels), where all simple squamous epithelium lining the heart and blood vessels dissolved molecules except for large proteins can pass from the is also called the endothelium. blood to the interstitial fl uid by traveling through gaps between adjacent epithelial cells. Transporting Epithelia Th e transporting epithelia actively In a tight epithelium, such as that in the kidney, adjacent and selectively regulate the exchange of nongaseous materials, cells are bound to each other by tight junctions that create a such as ions and nutrients, between the internal and external barrier, preventing substances from traveling between adjacent environments. Th ese epithelia line the hollow tubes of the diges- cells. To cross a tight epithelium, most substances must enter tive system and the kidney, where lumens open into the external the epithelial cells and go through them. Th e tightness of an epi- environment. Movement of material from the external environ- thelium is directly related to how selective it is about what can ment across the epithelium to the internal environment is called move across it. Some epithelia, such as those of the intestine, absorption. Movement in the opposite direction, from the inter- have the ability to alter the tightness of their junctions according nal to the external environment, is called secretion . to the body’s needs. Transporting epithelia can be identifi ed by the following characteristics ( Fig. 3.10 e): Types of Epithelia Structurally, epithelial tissues can be di- vided into two general types: (1) sheets of tissue that lie on the 1 Cell shape. Cells of transporting epithelia are much surface of the body or that line the inside of tubes and hollow thicker than cells of exchange epithelia, and they act as a organs and (2) secretory epithelia that synthesize and release barrier as well as an entry point. Th e cell layer is only one substances into the extracellular space. Histologists classify cell thick (a simple epithelium), but cells are cuboidal or sheet epithelia by the number of cell layers in the tissue and columnar. by the shape of the cells in the surface layer. Th is classifi cation 2 Membrane modifications. The apical membrane, the scheme recognizes two types of layering—simple (one cell surface of the epithelial cell that faces the lumen, has tiny thick) and stratifi ed (multiple cell layers) {stratum , layer + facere , finger-like projections called microvilli that increase the to make}—and three cell shapes— squamous { squama , fl attened surface area available for transport. A cell with microvilli plate or scale}, cuboidal, and columnar. However, physiologists has at least 20 times the surface area of a cell without them. are more concerned with the functions of these tissues, so in- In addition, the basolateral membrane, the side of the stead of using the histological descriptions, we will divide epi- epithelial cell facing the extracellular fl uid, may also have thelia into fi ve groups according to their function. folds that increase the cell’s surface area.

86 Fig. 3.10 ESSENTIALS

Types of Epithelia

(a) Exchange Epithelium

The thin, flat cells of Capillary epithelium exchange epithelium allow movement through Blood and between the cells. Capillary Pore Extracellular fluid

(b) Protective Epithelium (c) Ciliated Epithelium

Protective epithelia have Beating cilia create fluid many stacked layers of cells currents that sweep across that are constantly being the epithelial surface. replaced. This figure shows layers in skin (see Focus Cilia on Skin). Epithelial cells

Microvilli

SEM of the epithelial surface of an airway Section of skin showing cell layers. Golgi apparatus Nucleus Mitochondrion

Basal lamina

(d) Secretory Epithelium (e) Transporting Epithelium

Secretory epithelial cells make Transporting epithelia selectively and release a product. move substances between a Exocrine secretions, such as lumen and the ECF. the mucus shown here, are secreted outside the body. The secretions of endocrine Mucus Apical membrane Lumen of intestine or kidney cells (hormones) are released Microvilli into the blood. Tight junctions in a transporting epithelium prevent movement Transporting between adjacent epithelial cells. Substances must cell SEM of goblet cell instead pass through the epithelial cell, Golgi crossing two apparatus phospholipid cell membranes as they do so. Nucleus Basolateral membrane Goblet cells secrete mucus Extracellular fluid into the lumen of hollow organs such as the intestine.

87 Compartmentation: Cells and Tissues

3 Cell junctions. The cells of transporting epithelia are RUNNING PROBLEM firmly attached to adjacent cells by moderately tight to very tight junctions. Th is means that to cross the epithe- Many kinds of cancer develop in epithelial cells that are lium, material must move into an epithelial cell on one subject to damage or trauma. The cervix consists of two side of the tissue and out of the cell on the other side. types of epithelia. Secretory epithelium with mucus-secreting 4 Cell organelles. Most cells that transport materials have glands lines the inside of the cervix. A protective epithelium numerous mitochondria to provide energy for transport covers the outside of the cervix. At the opening of the cervix, processes. Th e properties of transporting epithelia diff er these two types of epithelia come together. In many cases, depending on where in the body the epithelia are located. infections caused by the human papillomavirus (HPV) cause For example, glucose can cross the epithelium of the small the cervical cells to develop dysplasia. Dr. Baird ran an HPV intestine and enter the extracellular fl uid but cannot cross test on Jan’s fi rst Pap smear, and it was positive for the virus. Today she is repeating the tests to see if Jan’s dysplasia and the epithelium of the large intestine. HPV infection have persisted. Th e transport properties of an epithelium can be regulated and modifi ed in response to various stimuli. Hormones, for ex- Q3: What other kinds of damage or trauma are cervical epithelial cells normally subjected to? Which of the two ample, affect the transport of ions by kidney epithelium. You types of cervical epithelia is more likely to be aff ected by will learn more about transporting epithelia when you study the physical trauma? kidney and digestive systems. Q4: The results of Jan’s fi rst Pap test showed atypical Ciliated Epithelia Ciliated epithelia are nontransporting squamous cells of unknown signifi cance (ASCUS). Were tissues that line the respiratory system and parts of the female these cells more likely to come from the secretory reproductive tract. Th e surface of the tissue facing the lumen portion of the cervix or from the protective epithelium? is covered with cilia that beat in a coordinated, rhythmic fash- ion, moving fl uid and particles across the surface of the tissue ( Fig. 3.10 c). Injury to the cilia or to their epithelial cells can stop space. Secretory cells may be scattered among other epithelial ciliary movement. For example, smoking paralyzes the ciliated cells, or they may group together to form a multicellular gland. epithelium lining the respiratory tract. Loss of ciliary function Th ere are two types of secretory glands: exocrine and endocrine. contributes to the higher incidence of respiratory infection in Exocrine glands release their secretions to the body’s ex- smokers, when the mucus that traps bacteria can no longer be ternal environment {exo - , outside + krinein, to secrete}. Th is swept out of the lungs by the cilia. may be onto the surface of the skin or onto an epithelium lining one of the internal passageways, such as the airways of the lung Protective Epithelia The protective epithelia prevent ex- or the lumen of the intestine ( Fig. 3.10 d). In eff ect, an exocrine change between the internal and external environments and secretion leaves the body. Th is explains how some exocrine se- protect areas subject to mechanical or chemical stresses. Th ese cretions, like stomach acid, can have a pH that is incompatible epithelia are stratifi ed tissues, composed of many stacked layers with life . of cells (Fig. 3.10 b). Protective epithelia are toughened by the Most exocrine glands release their products through open secretion of keratin { keras, horn}, the same insoluble protein tubes known as ducts. Sweat glands, mammary glands in the abundant in hair and nails. Th e epidermis { epi, upon + derma, breast, salivary glands, the liver, and the pancreas are all exo- skin} and linings of the mouth, pharynx, esophagus, urethra, crine glands. and vagina are all protective epithelia. Exocrine gland cells produce two types of secretions. Because protective epithelia are subjected to irritating Serous secretions are watery solutions, and many of them con- chemicals, bacteria, and other destructive forces, the cells in tain enzymes. Tears, sweat, and digestive enzyme solutions are them have a short life span. In deeper layers, new cells are pro- all serous exocrine secretions. Mucous secretions (also called duced continuously, displacing older cells at the surface. Each mucus) are sticky solutions containing glycoproteins and time you wash your face, you scrub off dead cells on the sur- proteoglycans. face layer. As skin ages, the rate of cell turnover declines. Treti- Goblet cells, shown in Figure 3.10 d, are single exocrine noin (Retin-A®), a drug derived from vitamin A, speeds up cell cells that produce mucus. Mucus acts as a lubricant for food to division and surface shedding so treated skin develops a more be swallowed, as a trap for foreign particles and microorganisms youthful appearance. inhaled or ingested, and as a protective barrier between the epi- thelium and the environment. Secretory Epithelia Secretory epithelia are composed of cells that produce a substance and then secrete it into the extracellular

88 Compartmentation: Cells and Tissues

Some exocrine glands contain more than one type of secre- transports the secretion to its destination (the external environ- tory cell, and they produce both serous and mucous secretions. ment). Endocrine glands lose the connecting cells and secrete For example, the salivary glands release mixed secretions. their hormones into the bloodstream. Unlike exocrine glands, endocrine glands are ductless and release their secretions, called hormones, into the body’s extra- cellular compartment ( Fig. 3.9 d). Hormones enter the blood for Concept Check Answers: End of Chapter distribution to other parts of the body, where they regulate or 18. List the fi ve functional types of epithelia. coordinate the activities of various tissues, organs, and organ systems. Some of the best-known endocrine glands are the pan- 19. Defi ne secretion. creas, the thyroid gland, the gonads, and the pituitary gland. For 20. Name two properties that distinguish endocrine glands from exocrine years, it was thought that all hormones were produced by cells glands. grouped together into endocrine glands. We now know that iso- 21. The basal lamina of epithelium contains the protein fi ber laminin. Are 3 lated endocrine cells occur scattered in the epithelial lining of the overlying cells attached by focal adhesions or hemidesmosomes? the digestive tract, in the tubules of the kidney, and in the walls of the heart. 22. You look at a tissue under a microscope and see a simple squamous Figure 3.11 shows the epithelial origin of endocrine epithelium. Can it be a sample of the skin surface? Explain. and exocrine glands. During development, epithelial cells grow 23. A cell of the intestinal epithelium secretes a substance into the downward into the supporting connective tissue. Exocrine extracellular fl uid, where it is picked up by the blood and carried to the glands remain connected to the parent epithelium by a duct that pancreas. Is the intestinal epithelium cell an endocrine or an exocrine cell?

During development, Epithelium the region of epithelium Connective Tissues Provide Support and Barriers destined to become Connective glandular tissue divides tissue Connective tissues , the second major tissue type, provide struc- downward into the tural support and sometimes a physical barrier that, along with underlying connective tissue. specialized cells, helps defend the body from foreign invaders such as bacteria. Th e distinguishing characteristic of connective tissues is the presence of extensive extracellular matrix contain- ing widely scattered cells that secrete and modify the matrix ( Fig. 3.12 ). Connective tissues include blood, the support tis- sues for the skin and internal organs, and cartilage and bone.

Structure of Connective Tissue The extracellular matrix of connective tissue is a ground substance of proteoglycans and water in which insoluble protein fi bers are arranged, much like pieces of fruit suspended in a gelatin salad. Th e consistency of Exocrine Endocrine ground substance is highly variable, depending on the type of connective tissue ( Fig. 3.12 a). At one extreme is the watery ma- Duct trix of blood, and at the other extreme is the hardened matrix Connecting of bone. In between are solutions of proteoglycans that vary in cells disappear consistency from syrupy to gelatinous. The term ground sub- Exocrine stance is sometimes used interchangeably with matrix . secretory cells Connective tissue cells lie embedded in the extracellular Endocrine matrix. Th ese cells are described as fi xed if they remain in one secretory cells place and as mobile if they can move from place to place. Fixed Blood vessel cells are responsible for local maintenance, tissue repair, and A hollow center, or lumen, Endocrine glands lose the energy storage. Mobile cells are responsible mainly for defense. forms in exocrine glands, connecting bridge of cells creating a duct that that links them to the Th e distinction between fi xed and mobile cells is not absolute, provides a passageway for parent epithelium. Their because at least one cell type is found in both fi xed and mobile secretions to move to the secretions go directly into surface of the epithelium. the bloodstream. forms. Although extracellular matrix is nonliving, the connective Fig. 3.11 Development of endocrine and exocrine glands from tissue cells constantly modify it by adding, deleting, or rearrang- epithelium. ing molecules. Th e suffi x -blast {blastos, sprout} on a connective

89 Fig. 3.12 ESSENTIALS

Connective Tissue CONNECTIVE TISSUE (a) Map of connective tissue components is composed of

Cells

Mobile Fixed

Blood cells

Red blood White blood Macrophages Adipocytes Fibroblasts cells cells

synthesize O2 and CO2 Fight invaders Store energy transport in fat

Matrix

can be divided into

Ground substance Protein fibers

Mineralized Gelatinous Syrupy Watery Fibronectin Fibrillin Elastin Collagen

Blood Connects cells Forms filaments Stretch and Stiff but Bone • Loose connective tissue to matrix and sheets recoil flexible • Dense connective tissue plasma • Cartilage • Adipose tissue

(b) Types of Connective Tissue

Tissue NameGround Substance Fiber Type and Arrangement Main Cell Types Where Found

Loose connective Gel; more ground substance Collagen, elastic, reticular; Fibroblasts Skin, around blood vessels tissue than fibers or cells random and organs, under epithelia

Dense, irregular More fibers than ground Mostly collagen; Fibroblasts Muscle and nerve sheaths connective tissue substance random

Dense, regular More fibers than ground Collagen; Fibroblasts Tendons and ligaments connective tissue substance parallel

Adipose tissue Very little ground substance None Brown fat and white fat Depends on age and sex

Blood Aqueous NoneBlood cells In blood and lymph vessels

Cartilage Firm but flexible; CollagenChondroblasts Joint surfaces, spine, ear, hyaluronic acid nose, larynx

Bone Rigid due to calcium salts CollagenOsteoblasts and Bones osteocytes

90 Compartmentation: Cells and Tissues tissue cell name oft en indicates a cell that is either growing or actively secreting extracellular matrix. Fibroblasts, for example, BIOTECHNOLOGY are connective tissue cells that secrete collagen-rich matrix. Cells that are actively breaking down matrix are identifi ed by the suffi x -clast { klastos, broken}. Cells that are neither growing, Grow Your Own Cartilage secreting matrix components, nor breaking down matrix may Have you torn the cartilage in your knee playing bas- be given the suffi x - cyte, meaning “cell.” Remembering these suf- ketball or some other sport? Maybe you won’t need surgery fi xes should help you remember the functional diff erences be- to repair it. Replacing lost or damaged cartilage is moving tween cells with similar names, such as the osteoblast, osteocyte, from the realm of science fi ction to the realm of reality. Re- and osteoclast, three cell types found in bone. searchers have developed a process in which they take a car- In addition to secreting proteoglycan ground substance, tilage sample from a patient and put it into a tissue culture connective tissue cells produce matrix fi bers. Four types of fi ber medium to reproduce. Once the culture has grown enough chondrocytes —the cells that synthesize the extracellular ma- 3 proteins are found in matrix, aggregated into insoluble fi bers. + trix of cartilage—the mixture is sent back to a physician, who Collagen { kolla, glue - genes, produced} is the most abun- surgically places the cells in the patient’s knee at the site of dant protein in the human body, almost one-third of the body’s cartilage damage. Once returned to the body, the chondro- dry weight. Collagen is also the most diverse of the four protein cytes secrete matrix and help repair the damaged cartilage. types, with at least 12 variations. It is found almost everywhere Because the person’s own cells are grown and reimplanted, connective tissue is found, from the skin to muscles and bones. there is no tissue rejection. A diff erent method for cartilage Individual collagen molecules pack together to form collagen fi - repair being used outside the United States is treatment bers, fl exible but inelastic fi bers whose strength per unit weight with stem cells derived from bone marrow. Both therapies exceeds that of steel. Th e amount and arrangement of collagen have proved to be eff ective treatments for selected cartilage fibers help determine the mechanical properties of different problems. types of connective tissues. Th ree other protein fi bers in connective tissue are elastin, fi - brillin, and fi bronectin. Elastin is a coiled, wavy protein that re- fl exible, and notable for its lack of blood supply. Without a blood turns to its original length aft er being stretched. Th is property is supply, nutrients and oxygen must reach the cells of cartilage by known as elastance . Elastin combines with the very thin, straight fi - diff usion. Th is is a slow process, which means that damaged car- bers of fi brillin to form fi laments and sheets of elastic fi bers. Th ese tilage heals slowly. two fi bers are important in elastic tissues such as the lungs, blood Th e fi brous extracellular matrix of bone is said to be cal- vessels, and skin. As mentioned earlier, fi bronectin connects cells cifi ed because it contains mineral deposits, primarily calcium to extracellular matrix at focal adhesions. Fibronectins also play an salts, such as calcium phosphate ( Fig. 3.13 b). These minerals important role in wound healing and in blood clotting. give the bone strength and rigidity. Adipose tissue is made up of adipocytes, or fat cells. An Types of Connective Tissue Figure 3.12 b compares the prop- adipocyte of white fat typically contains a single enormous lipid erties of different types of connective tissue. The most com- droplet that occupies most of the volume of the cell (Fig. 3.13 e). mon types are loose and dense connective tissue, adipose tissue, Th is is the most common form of adipose tissue in adults. blood, cartilage, and bone. By many estimates, connective tis- Brown fat is composed of adipose cells that contain mul- sues are the most abundant of the tissue types as they are a com- tiple lipid droplets rather than a single large droplet. Th is type of ponent of most organs. fat has been known for many years to play an important role in Loose connective tissues ( Fig. 3.13 a) are the elastic tis- temperature regulation in infants. Until recently it was thought sues that underlie skin and provide support for small glands. to be almost completely absent in adults. However, modern im- Dense connective tissues provide strength or flexibility. Ex- aging techniques such as combined CT and PET scans have re- amples are tendons, ligaments, and the sheaths that surround vealed that adults do have brown fat . muscles and nerves. In these dense tissues, collagen fi bers are Blood is an unusual connective tissue that is characterized the dominant type. Tendons ( Fig. 3.13 c) attach skeletal muscles by its watery extracellular matrix called plasma . Plasma consists to bones. Ligaments connect one bone to another. Because liga- of a dilute solution of ions and dissolved organic molecules, in- ments contain elastic fi bers in addition to collagen fi bers, they cluding a large variety of soluble proteins. Blood cells and cell have a limited ability to stretch. Tendons lack elastic fi bers and fragments are suspended in the plasma (Fig. 3.13 d), but the so cannot stretch. insoluble protein fi bers typical of other connective tissues are Cartilage and bone together are considered support- absent. ing connective tissues. Th ese tissues have a dense ground sub- stance that contains closely packed fi bers. Cartilage is found in structures such as the nose, ears, knee, and windpipe. It is solid,

91 Fig. 3.13 ESSENTIALS

Types of Connective Tissue

(a) Loose Connective Tissue Loose connective tissue is very flexible, with Fibroblasts are Elastic fibers multiple cell types and cells that secrete matrix proteins. fibers. Ground substance Collagen fibers is the matrix of loose connective tissue.

Free macrophage Light micrograph of loose connective tissue

(b) Bone and Cartilage (c) Dense Regular Connective Tissue

Hard bone forms when osteo- Collagen fibers of tendon blasts deposit calcium phosphate are densely packed into crystals in the matrix. Cartilage parallel bundles. has firm but flexible matrix secreted by cells called chondrocytes.

Collagen fibers Matrix

Light micrograph of bone

Chondrocytes

Matrix Light micrograph of tendon

Light micrograph of hyaline cartilage

(d) Blood (e) Adipose Tissue

Blood consists of liquid matrix (plasma) plus red and In white fat, the cell cytoplasm is white blood cells and the cell fragments called platelets. almost entirely filled with lipid droplets.

Red blood cell Platelet

Lymphocyte White Nucleus Blood Neutrophil Cells Lipid droplets Eosinophil

Light micrograph Light micrograph of a blood smear of adipose tissue

92 Compartmentation: Cells and Tissues

Muscle tissue has the ability to contract and produce force Concept Check Answers: End of Chapter and movement. Th e body contains three types of muscle tissue: 24. What is the distinguishing characteristic of connective tissues? cardiac muscle in the heart; smooth muscle, which makes up 25. Name four types of protein fi bers found in connective tissue matrix and most internal organs; and skeletal muscle. Most skeletal muscles give the characteristics of each. attach to bones and are responsible for gross movement of the body. 26. Name six types of connective tissues. Neural tissue has two types of cells. Neurons, or nerve 27. Blood is a connective tissue with two components: plasma and cells. cells, carry information in the form of chemical and electrical Which of these is the matrix in this connective tissue? signals from one part of the body to another. Th ey are concen- 28. Why does torn cartilage heal more slowly than a cut in the skin? trated in the brain and spinal cord but also include a network of cells that extends to virtually every part of the body. Glial cells, or neuroglia, are the support cells for neurons. A summary 3 of the characteristics of the four tissue types can be found in Muscle and Neural Tissues Are Excitable Table 3.4 . Th e third and fourth of the body’s four tissue types—muscle and neural—are collectively called the excitable tissues because of their ability to generate and propagate electrical signals called action potentials. Both of these tissue types have minimal extra- Tissue Remodeling cellular matrix, usually limited to a supportive layer called the Most people associate growth with the period from birth to external lamina. Some types of muscle and nerve cells are also adulthood. However, cell birth, growth, and death continue notable for their gap junctions, which allow the direct and rapid throughout a person’s life. Th e tissues of the body are constantly conduction of electrical signals from cell to cell. remodeled as cells die and are replaced.

Table Characteristics of the Four Tissue Types 3.4

Epithelial Connective Muscle Nerve

Matrix amount Minimal Extensive Minimal Minimal

Matrix type Basal lamina Varied—protein fibers External lamina External lamina in ground substance that ranges from liquid to gelatinous to firm to calcified

Unique features No direct blood Cartilage has no Able to generate Able to generate supply blood supply electrical signals, electrical signals force, and movement

Surface features of cells Microvilli, cilia N/A N/A N/A

Locations Covers body surface; Supports skin Makes up skeletal Throughout body; lines cavities and and other organs; muscles, hollow concentrated in brain hollow organs, and cartilage, bone, and organs, and tubes and spinal cord tubes; secretory blood glands

Cell arrangement and Variable number of Cells not in layers; Cells linked in Cells isolated or shapes layers, from one to usually randomly sheets or elongated networked; cell many; cells flattened, scattered in matrix; bundles; cells shaped appendages highly cuboidal, or columnar cell shape irregular to in elongated, thin branched and/or round cylinders; heart elongated muscle cells may be branched

93 Compartmentation: Cells and Tissues

Apoptosis Is a Tidy Form of Cell Death RUNNING PROBLEM Cell death occurs two ways, one messy and one tidy. In necrosis, The day after Jan’s visit, the computerized cytology analysis cells die from physical trauma, toxins, or lack of oxygen when system rapidly scans the cells on the slide of Jan’s cervical their blood supply is cut off . Necrotic cells swell, their organ- tissue, looking for abnormal cell size or shape. The computer elles deteriorate, and fi nally the cells rupture. Th e cell contents is programmed to fi nd multiple views for the cytologist released this way include digestive enzymes that damage adja- to evaluate. The results of Jan’s two Pap tests are shown in cent cells and trigger an infl ammatory response. You see necro- Figure 3.14 . sis when you have a red area of skin surrounding a scab. In contrast, cells that undergo programmed cell death, or Q5: Has Jan’s dysplasia improved or worsened? What apoptosis {ap-oh-TOE-sis or a-pop-TOE-sis; apo -, apart, away evidence do you have to support your answer? + ptosis, falling}, do not disrupt their neighbors when they die. Q6: Use your answer to question 5 to predict whether Jan’s Apoptosis, also called cell suicide, is a complex process regulated HPV infection has persisted or been cleared by her by multiple chemical signals. Some signals keep apoptosis from immune system. occurring, while other signals tell the cell to self-destruct. When the suicide signal wins out, chromatin in the nucleus condenses, and the cell pulls away from its neighbors. It shrinks, then breaks up into tidy membrane-bound blebs that are gobbled up by Stem Cells Can Create New Specialized Cells neighboring cells or by wandering cells of the immune system. Apoptosis is a normal event in the life of an organism. If cells in the adult body are constantly dying, where do their During fetal development, apoptosis removes unneeded cells, replacements come from? Th is question is still being answered such as half the cells in the developing brain and the webs of and is one of the hottest topics in biological research today. Th e skin between fi ngers and toes. In adults, cells that are subject to following paragraphs describe what we currently know. wear and tear from exposure to the outside environment may All cells in the body are derived from the single cell formed live only a day or two before undergoing apoptosis. For example, at conception. Th at cell and those that follow reproduce them- it has been estimated that the intestinal epithelium is completely selves by undergoing the cell division process known as mitosis replaced with new cells every two to fi ve days. [see Appendix C ]. Th e very earliest cells in the life of a human being are said to be totipotent { totus, entire} because they have the ability to develop into any and all types of specialized cells. Concept Check A nswers: End of Chapter Any totipotent cell has the potential to become a functioning organism. 29. What are some features of apoptosis that distinguish it from cell death due to injury?

Fig. 3.14 Pap smears of cervical cells. The darker-staining structures inside the cells are the nuclei, surrounded by lighter-staining cytoplasm.

94 Fig. 3.15 FOCUS ON ...

The Skin

The layers of the skin

Hair follicles secrete the Sebaceous glands are Arrector pili muscles pull nonliving keratin shaft of exocrine glands that hair follicles into a vertical hair. secrete a lipid mixture. position when the muscle contracts, creating "goose Sweat glands secrete a dilute bumps." salt fluid to cool the body.

Sensory receptors monitor external conditions.

Epidermis consists of multiple cell layers that create a protective barrier.

The dermis is loose connective tissue that contains exocrine glands, blood vessels, muscles, and nerve endings.

Hypodermis contains adipose Artery Vein tissue for insulation. Blood vessels extend Epidermis upward into the dermis. The skin surface is a mat of Sensory nerve linked keratin fibers left behind when old epithelial cells die. Apocrine glands in the genitalia, anus, axillae (axilla, armpit), and eyelids release Phospholipid matrix acts as the waxy or viscous milky secretions in skin's main waterproofing agent. response to fear or sexual excitement. Surface keratinocytes produce keratin fibers.

Desmosomes anchor epithelial cells to each other. CLINICAL FOCUS Epidermal cell Melanoma is a serious Melanocytes contain form of skin cancer the pigment melanin. Melanoma occurs when melanocytes become malignant, often following repeated exposure Basal lamina to UV light. One study found that people who used tanning beds were 24% more likely to develop melanoma.

Connection between epidermis and dermis

Hemidesmosomes tie epidermal cells to fibers of the basal lamina.

Basal lamina or basement membrane is an acellular layer between epidermis and dermis.

95 Compartmentation: Cells and Tissues

Aft er about day 4 of development, the totipotent cells of differentiate and what type of cell to become. And even once the embryo begin to specialize, or diff erentiate. As they do so, these two challenges are overcome and donor stem cells are im- they narrow their potential fates and become pluripotent planted, the body may recognize that the new cells are foreign {plures, many}. Pluripotent cells can develop into many diff erent tissue and try to reject them. cell types but not all cell types. An isolated pluripotent cell can- Stem cell research is an excellent example of the dynamic not develop into an organism. and oft en controversial nature of science. For the latest research As diff erentiation continues, pluripotent cells develop into fi ndings, as well as pending legislation and laws regulating stem the various tissues of the body. As the cells specialize and mature, cell research and use, check authoritative web sites, such as many lose the ability to undergo mitosis and reproduce them- that sponsored by the U.S. National Institutes of Health (http:// selves. Th ey can be replaced, however, by new cells created from stemcells.nih.gov ). stem cells, less specialized cells that retain the ability to divide. Undiff erentiated stem cells in a tissue that retain the ability to divide and develop into the cell types of that tissue are said to be Organs multipotent { multi, many}. Some of the most-studied multipotent Groups of tissues that carry out related functions may form adult stem cells are found in bone marrow and give rise to blood structures known as organs. Th e organs of the body contain the cells. However, all adult stem cells occur in very small numbers. four types of tissue in various combinations. Th e skin is an ex- Th ey are diffi cult to isolate and do not thrive in the laboratory. cellent example of an organ that incorporates all four types of Biologists once believed that nerve and muscle cells, which tissue into an integrated whole. We think of skin as a thin layer are highly specialized in their mature forms, could not be re- that covers the external surfaces of the body, but in reality it is placed when they died. Now research indicates that stem cells the heaviest single organ, at about 16% of an adult’s total body for these tissues do exist in the body. However, naturally occur- weight! If it were fl attened out, it would cover a surface area of ring neural and muscle stem cells are so scarce that they can- between 1.2 and 2.3 square meters, about the size of a couple of not replace large masses of dead or dying tissue that result from card-table tops. Its size and weight make skin one of the most diseases such as strokes or heart attacks. Consequently, one goal important organs of the body. of stem cell research is to fi nd a source of pluripotent or multi- As we consider the systems of the body in the succeeding potent stem cells that could be grown in the laboratory. If stem chapters, you will see how diverse cells, tissues, and organs carry cells could be gown in larger numbers, they could be implanted out the processes of the living body. Although the body’s cells to treat damaged tissues and degenerative diseases, those in have diff erent structures and diff erent functions, they have one which cells degenerate and die. need in common: a continuous supply of energy. Without energy, One example of a degenerative disease is Parkinson’s dis- cells cannot survive, let alone carry out all the other processes of ease, in which certain types of nerve cells in the brain die. Em- daily living. bryos and fetal tissue are rich sources of stem cells, but the use of embryonic stem cells is controversial and poses many legal and ethical questions. Some researchers hope that adult stem cells will show plasticity, the ability to specialize into a cell of a type diff erent from the type for which they were destined. Th ere are still many challenges facing us before stem cell therapy becomes a standard medical treatment. One is find- ing a good source of stem cells. A second major challenge is determining the chemical signals that tell stem cells when to

RUNNING PROBLEM CONCLUSION

The Pap Test, Cervical Cancer, and HPV In this running problem, you learned that the Pap test can papillomavirus (HPV), a common sexually transmitted detect the early cell changes that precede cervical cancer. infection, can also cause cervical dysplasia. In most cases, The diagnosis is not always simple because the change the woman’s immune system overcomes the virus within in cell cytology from normal to cancerous occurs along a two years, and the cervical cells revert to normal. A small continuum and can be subject to individual interpretation. number of women with persistent HPV infections have In addition, not all cell changes are cancerous. The human a higher risk of developing cervical cancer, however.

96 Compartmentation: Cells and Tissues

RUNNING PROBLEM CONCLUSION (continued)

Studies indicate that 98% of cervical cancers are associated for HPV. This site also contains information about cervical with HPV infection. To learn more about the association cancer. To check your understanding of the running between HPV and cervical cancer, go to the National problem, compare your answers with the information in Cancer Institute homepage (www.cancer.gov) and search the following summary table.

Question Facts Integration and Analysis

1. Why does the treatment of cancer Cancerous cells divide uncontrollably and Unless removed, cancerous cells will focus on killing the cancerous cells? fail to coordinate with normal cells. Cancer- displace normal cells. This may cause ous cells fail to diff erentiate into specialized destruction of normal tissues. In addi- 3 cells. tion, because cancerous cells do not become specialized, they cannot carry out the same functions as the special- ized cells they displace.

2. What is happening in cancer cells that Cancerous cells divide uncontrollably. Divid- Actively reproducing cells are likely explains the large size of their nucleus ing cells must duplicate their DNA prior to to have more DNA in their nucleus as and the relatively small amount of cell division, and this DNA duplication takes they prepare to divide, so their nuclei cytoplasm? place in the nucleus, leading to the large size tend to be larger. Each cell division of that organelle. splits the cytoplasm between two daughter cells. If division is occurring rapidly, the daughter cells may not have time to synthesize new cyto- plasm, so the amount of cytoplasm is less than in a normal cell.

3. What other kinds of damage or The cervix is the passageway between the The cervix is subject to trauma or trauma are cervical epithelial cells nor- uterus and vagina. damage, such as might occur during mally subjected to? sexual intercourse and childbirth.

4. Which of its two types of epithelia is The cervix consists of secretory epithelium Protective epithelium is composed of more likely to be aff ected by trauma? with mucus-secreting glands lining the in- multiple layers of cells and is designed side and protective epithelium covering the to protect areas from mechanical and outside. chemical stress. Therefore, the secre- tory epithelium with its single-cell layer is more easily damaged.

5. Jan’s fi rst Pap test showed atypical Secretory cells are columnar epithelium. Pro- Protective epithelium with multiple squamous cells of unknown signifi cance tective epithelium is composed of multiple cell layers has cells that are fl at (strati- (ASCUS). Were these cells more likely cell layers. fi ed squamous epithelium). The desig- to come from the secretory portion nation ASC refers to these protective of the cervix or from the protective epithelial cells. epithelium?

6. Has Jan’s dysplasia improved or wors- The slide from Jan’s fi rst Pap test shows The disappearance of the abnormal ened? What evidence do you have to abnormal cells with large nuclei and little cy- cells indicates that Jan’s dysplasia has support your answer? toplasm. These abnormal cells do not appear resolved. She will return in six months in the second test. for a repeat Pap test. If it shows no dysplasia, her cervical cells have re- verted to normal.

7. Use your answer to question 5 to The cells in the second Pap test appear Once Jan’s body fi ghts off the HPV predict whether Jan’s HPV infection has normal. infection, her cervical cells should persisted or been cleared by her im- revert to normal. Her second HPV test mune system. showed no evidence of HPV DNA.

97 Compartmentation: Cells and Tissues

Test your understanding with: • Practice Tests • PhysioExTM Lab Simulations • Running Problem Quizzes • Interactive Physiology TM • A&PFlix Animations Animations www.masteringaandp.com

Chapter Summary

Cell biology and histology illustrate one of the major themes in physiol- interactions that create the mechanical properties of cells and tissues. Pro- ogy: compartmentation . In this chapter you learned how a cell is sub- tein fi bers of the cytoskeleton and cell junctions, along with the mol- divided into two main compartments, the nucleus and the cytoplasm. ecules that make up the extracellular matrix, form the “glue” that holds You also learned how cells form tissues that create larger compart- tissues together. ments within the body. A second theme in this chapter is the molecular

Functional Compartments of the Body 12. Ribosomes are inclusions that take part in protein synthesis. 13. Insoluble protein fi bers come in three sizes: actin fi bers (also called Fluids and Electrolytes:Electrolytes: Introduction to BodyBody FluidFluidss microfi laments ), intermediate fi laments, and microtubules. ( Ta- ble 3.2 ) 1. Th e cell is the functional unit of living organisms. 14. Centrioles that aid the movement of chromosomes during cell divi- 2. Th e major human body cavities are the cranial cavity (skull), tho- sion, cilia that move fl uid or secretions across the cell surface, and racic cavity (thorax), and abdominopelvic cavity. (Fig. 3.1 a) fl agella that propel sperm through body fl uids are made of microtu- 3. Th e lumens of some hollow organs are part of the body’s external bules. ( Figures 3.4 e, 3.5) environment. 15. Th e changeable cytoskeleton provides strength, support, and inter- 4. Th e body fl uid compartments are the extracellular fl uid (ECF) out- nal organization; aids transport of materials within the cell; links side the cells and the intracellular fl uid (ICF) inside the cells. Th e cells together; and enables motility in certain cells. (Fig. 3.4 b) ECF can be subdivided into interstitial fl uid bathing the cells and 16. Motor proteins such as myosins, kinesins, and dyneins associate plasma, the fl uid portion of the blood. ( Fig. 3.1 b) with cytoskeleton fi bers to create movement. ( Fig. 3.6 ) 17. Membranes around organelles create compartments that separate Biological Membranes functions. 5. Th e word membrane is used both for cell membranes and for tissue 18. Mitochondria generate most of the cell’s ATP. ( Fig. 3.4 g) membranes that line a cavity or separate two compartments. (Fig. 19. Th e smooth endoplasmic reticulum is the primary site of lipid syn- 3.1 c) thesis. Th e rough endoplasmic reticulum is the primary site of pro- 6. Th e cell membrane acts as a barrier between the intracellular and tein synthesis. ( Fig. 3.4 i) extracellular fluids, provides structural support, and regulates 20. Th e Golgi apparatus packages proteins into vesicles. Secretory ves- exchange and communication between the cell and its environment. icles release their contents into the extracellular fl uid. ( Fig. 3.4 h) 7. The fluid mosaic model of a biological membrane shows it as a 21. Lysosomes and peroxisomes are small storage vesicles that contain phospholipid bilayer with proteins inserted into the bilayer. (Fig. digestive enzymes. ( Fig. 3.4 c and d) 3.2 b) 22. The nucleus contains DNA, the genetic material that ultimately 8. Membrane lipids include phospholipids, sphingolipids, and choles- controls all cell processes, in the form of chromatin. Th e double- terol. Lipid-anchored proteins attach to membrane lipids. membrane nuclear envelope surrounding the nucleus has nuclear 9. Transmembrane proteins are integral proteins tightly bound to the pore complexes that allow controlled chemical communication be- phospholipid bilayer. Peripheral proteins attach less tightly to ei- tween the nucleus and cytosol. Nucleoli are nuclear areas that con- ther side of the membrane. (Fig. 3.2 b, c) trol the synthesis of RNA for ribosomes. (Fig. 3.4 j) 10. Carbohydrates attach to the extracellular surface of cell membranes. 23. Protein synthesis is an example of how the cell separates functions by isolating them to separate compartments within the cell ( Fig. 3.7 ) Intracellular Compartments Tissues of the Body 11. Th e cytoplasm consists of semi-gelatinous cytosol with dissolved nutrients, ions, and waste products. Suspended in the cytosol are the

other components of the cytoplasm: insoluble inclusions and fi bers, Muscular: AnatomyAnatomy Review—Skeletal Muscle Tissue which have no enclosing membrane, and organelles, which are 24. Th ere are four primary tissue types in the human body: epithelial, membrane-enclosed bodies that carry out specifi c functions. (Fig. connective, muscle, and neural. 3.4 a)

98 Compartmentation: Cells and Tissues

25. Extracellular matrix secreted by cells provides support and a means 32. Connective tissues have extensive extracellular matrix that provides of cell-cell communication. It is composed of proteoglycans and in- structural support and forms a physical barrier. (Fig. 3.12 ) soluble protein fi bers. 33. Loose connective tissues are the elastic tissues that underlie skin. 26. Animal cell junctions fall into three categories. Gap junctions al- Dense connective tissues, including tendons and ligaments, have low chemical and electrical signals to pass directly from cell to cell. strength or fl exibility because they are made of collagen. Adipose Tight junctions restrict the movement of material between cells. tissue stores fat. Th e connective tissue we call blood is characterized Anchoring junctions hold cells to each other or to the extracellular by a watery matrix. Cartilage is solid and fl exible and has no blood matrix. ( Fig. 3.8 ) supply. Th e fi brous matrix of bone is hardened by deposits of cal- 27. Membrane proteins called cell adhesion molecules (CAMs) are es- cium salts. ( Fig. 3.13 ) sential in cell adhesion and in anchoring junctions. (Table 3.3 ) 34. Muscle and neural tissues are called excitable tissues because of 28. Desmosomes and adherens junctions anchor cells to each other. their ability to generate and propagate electrical signals called ac- Focal adhesions and hemidesmosomes anchor cells to matrix. ( Fig. tion potentials. Muscle tissue has the ability to contract and pro- 3.8 ) duce force and movement. Th ere are three types of muscle: cardiac, 29. Epithelial tissues protect the internal environment, regulate the ex- smooth, and skeletal. 3 change of material, or manufacture and secrete chemicals. Th ere are 35. Neural tissue includes neurons, which use electrical and chemical fi ve functional types found in the body: exchange, transporting, cili- signals to transmit information from one part of the body to an- ated, protective, and secretory. (Fig. 3.9 ) other, and support cells known as glial cells (neuroglia). 30. Exchange epithelia permit rapid exchange of materials, particu- Tissue Remodeling larly gases. Transporting epithelia actively regulate the selective ex- change of nongaseous materials between the internal and external 36. Cell death occurs by necrosis, which adversely aff ects neighboring environments. Ciliated epithelia move fl uid and particles across the cells, and by apoptosis, programmed cell death that does not dis- surface of the tissue. Protective epithelia help prevent exchange be- turb the tissue. tween the internal and external environments. Th e secretory epithe- 37. Stem cells are cells that are able to reproduce themselves and dif- lia release secretory products into the external environment or the ferentiate into specialized cells. Stem cells are most plentiful in em- blood. (Fig. 3.10 ) bryos but are also found in the adult body. 31. Exocrine glands release their secretions into the external environ- Organs ment through ducts. Endocrine glands are ductless glands that release their secretions, called hormones, directly into the extracel- 38. Organs are formed by groups of tissues that carry out related func- lular fl uid. ( Fig. 3.9 b) tions. The organs of the body contain the four types of tissues in various ratios. For example, skin is largely connective tissue.

Questions

Level One Reviewing Facts and Terms 7. Exocrine glands produce watery secretions (such as tears or sweat) called , or stickier solutions called . 1. List the four general functions of the cell membrane. 8. Match each organelle with its function: 2. In 1972, Singer and Nicolson proposed the fl uid mosaic model of the cell membrane. According to this model, the membrane is composed (a) endoplasmic reticulum 1. powerhouse of the cell where of a bilayer of and a variety of embedded , (b) Golgi apparatus most ATP is produced with on the extracellular surface. (c) lysosome 2. degrades long-chain fatty acids 3. What are the two primary types of biomolecules found in the cell (d) mitochondrion and toxic foreign molecules membrane? (e) peroxisome 3. network of membranous tubules 4. D e fi ne and distinguish between inclusions and organelles. Give an that synthesize biomolecules example of each. 4. digestive system of cell, degrading 5. D e fi ne cytoskeleton. List fi ve functions of the cytoskeleton. or recycling components 5. modifi es and packages proteins 6. Match each term with the description that fi ts it best: into vesicles (a) cilia 1. in human cells, appears as single, long, 9. What process activates the enzymes inside lysosomes? (b) centriole whiplike tail (c) fl agellum 2. short, hairlike structures that beat to 10. glands release hormones, which enter the blood and (d) centrosome produce currents in fl uids regulate the activities of organs or systems. 3. a bundle of microtubules that aids in 11. List the four major tissue types. Give an example and location of mitosis each. 4. the microtubule-organizing center 12. Th e largest and heaviest organ in the body is the .

99 Compartmentation: Cells and Tissues

13. Match each protein to its function. Functions in the list may be used 21. Sketch a short series of columnar epithelial cells. Label the apical more than once. and basolateral borders of the cells. Briefly explain the different kinds of junctions found on these cells. (a) cadherin 1. membrane protein used to form cell 22. Arrange the following compartments in the order a glucose mol- (b) CAM junctions ecule entering the body at the intestine would encounter them: (c) collagen 2. matrix glycoprotein used to anchor cells interstitial fluid, plasma, intracellular fluid. Which of these fluid (d) connexin 3. protein found in gap junctions compartments is/are considered extracellular fl uid(s)? (e) elastin 4. matrix protein found in connective tissue (f) fi brillin 23. Explain how inserting cholesterol into the phospholipid bilayer of (g) fi bronectin the cell membrane decreases membrane permeability. (h) integrin 24. Compare and contrast the structure, locations, and functions of (i) occludin bone and cartilage. 25. D i ff erentiate between the terms in each set below: 14. What types of glands can be found within the skin? Name the secre- (a) lumen and wall tion of each type. (b) cytoplasm and cytosol 15. Th e term matrix can be used in reference to an organelle or to tis- (c) myosin and keratin sues. Compare the meanings of the term in these two contexts. 26. When a tadpole turns into a frog, its tail shrinks and is reab- Level Two Reviewing Concepts sorbed. Is this an example of necrosis or apoptosis? Defend your answer. 16. List, compare, and contrast the three types of cell junctions and 27. Match the structures from the chapter to the basic physiological their subtypes. Give an example of where each type can be found in themes in the right column and give an example or explanation the body and describe its function in that location. for each match. A structure may match with more than one theme. 17. Which would have more rough endoplasmic reticulum: pancreatic cells that manufacture the protein hormone insulin, or adrenal cor- (a) cell junctions 1. communication tex cells that synthesize the steroid hormone cortisol? (b) cell membrane 2. molecular interactions 18. A number of organelles can be considered vesicles. Defi ne vesicle (c) cytoskeleton 3. compartmentation and describe at least three examples. (d) organelles 4. mechanical properties 19. Explain why a stratifi ed epithelium off ers more protection than a (e) cilia 5. biological energy use simple epithelium. 20. Mapping exercise: Transform this list of terms into a map of cell 28. In some instances, the extracellular matrix can be quite rigid. How structure. Add functions where appropriate. might developing and expanding tissues cope with a rigid matrix to make space for themselves? • actin • microfi lament • cell membrane • microtubule Level Three Problem Solving • centriole • mitochondria 29. One result of cigarette smoking is paralysis of the cilia that line • cilia • nonmembranous organelle the respiratory passageways. What function do these cilia serve? • cytoplasm • nucleus Based on what you have read in this chapter, why is it harmful • cytoskeleton • organelle when they no longer beat? What health problems would you ex- • cytosol • peroxisome pect to arise? How does this explain the hacking cough common • extracellular matrix • ribosome among smokers? • fl agella • rough ER 30. Cancer is abnormal, uncontrolled cell division. What property of • Golgi apparatus • secretory vesicle epithelial tissues might (and does) make them more prone to devel- • intermediate fi lament • smooth ER oping cancer? • keratin • storage vesicle 31. What might happen to normal physiological function if matrix me- • lysosome • tubulin talloproteinases are inhibited by drugs?

Answers

5. Cytoplasmic fi bers are actin fi bers (microfi laments), intermediate Answers to Concept Check Questions fi laments, and microtubules. 6. Without a fl agellum, a sperm would be unable to swim to fi nd an 1. Membrane lipids are phospholipid, sphingolipid, and cholesterol. egg to fertilize. 2. Integral proteins are tightly bound to the membrane. Peripheral 7. Cytoplasm is everything inside the cell membrane except the nu- proteins are loosely bound to membrane components. Proteins cleus. Cytosol is the semi-gelatinous substance in which organelles may be transmembrane, lipid-anchored, or loosely bound to other and inclusions are suspended. proteins. 8. Cilia are short, usually are very numerous on a cell, and move fl uid 3. The tails of phospholipids are hydrophobic, and a single layer or substances across the cell surface. Flagella are longer, usually occur would put the tails in direct contact with aqueous body fl uids. singly on human sperm, and are used to propel a cell through a fl uid. 4. A substance crosses one phospholipid bilayer to enter a cell. 9. Motor proteins use energy to create movement.

100 Compartmentation: Cells and Tissues

10. A membrane separates organelles from the cytosol; inclusions are 21. Hemidesmosomes attach to laminin (see Fig. 3.8 ). suspended in the cytosol. 22. No, skin has many layers of cells in order to protect the internal en- 11. Rough ER has ribosomes attached to the cytoplasmic side of its vironment. A simple squamous epithelium (which is one cell thick membrane; smooth ER lacks ribosomes. Rough ER synthesizes with fl attened cells) would not be a protective epithelium. proteins; smooth ER synthesizes lipids. 23. Th e cell is an endocrine cell because it secretes its product into the 12. Lysosomes contain enzymes that break down bacteria and old or- extracellular space for distribution in the blood. ganelles. Peroxisomes contain enzymes that break down fatty acids 24. Connective tissues have extensive matrix. and foreign molecules. 25. Collagen provides strength and fl exibility; elastin and fi brillin pro- 13. Th e membranes of organelles create compartments that physically vide elastance; fi bronectin helps anchor cells to matrix. isolate their lumens from the cytosol. Th e double membrane of mi- 26. Connective tissues include bone, cartilage, blood, dense connective tochondria creates two diff erent compartments inside the organelle. tissues (ligaments and tendons), loose connective tissue, and adi- 14. A large number of mitochondria suggests that the cell has a high pose tissue. energy requirement because mitochondria are the site of greatest 27. Th e plasma, or liquid portion of blood, surrounds the blood cells 3 energy production in the cell. and is therefore the extracellular matrix. 15. Large amounts of smooth endoplasmic reticulum suggest that the 28. Cartilage lacks a blood supply, so oxygen and nutrients needed for tissue synthesizes large amounts of lipids, fatty acids, or steroids, or repair must reach the cells by diff usion, a slow process. that it detoxifi es foreign molecules. 16. Cell junctions are gap (communicating), tight (occluding), and 29. Apoptosis is a tidy form of cell death that removes cells without dis- anchoring. rupting their neighbors. By contrast, necrosis releases digestive en- zymes that damage neighboring cells. 17. (a) tight, (b) gap, (c) anchoring (specifi cally, desmosome), (d) an- choring (specifi cally, focal adhesion) 18. The five functional types of epithelia are protective, secretory, transporting, ciliated, and exchange. Answers to FFigureigure QuestQuestionsions 19. Secretion is the process by which a cell releases a substance into its Figure 3.9 : Endocrine glands (without ducts) secrete their hormones environment. into the blood. Exocrine glands, with ducts, secrete their products 20. Endocrine glands do not have ducts, and they secrete into the outside the body—onto the surface of the skin or into the lumen of an blood. Exocrine glands have ducts and secrete into the external organ that opens into the environment outside the body. environment.

101 Compartmentation: Cells and Tissues

Answers to Review Questions

Level One Reviewing Facts and Terms 19. Stratified has many cell layers for protection; simple epithelium only has one 1. Create a barrier between cell and ECF; regulate exchange of material be- layer. tween cell and ECF; transfer information between the cell and other cells; 20. Map: See Figure 3.2. provide structural support. 21. See Figure 3.10e. Tight junctions prevent movement of material between 2. phospholipids; proteins; carbohydrates cells; leaky junctions allow some material to pass between cells. 3. phospholipids and proteins 22. intracellular fluid; interstitial fluid; plasma. Interstitial fluid and plasma are ECF. 4. Inclusions: particles of insoluble material, such as glycogen and ribosomes. 23. Cholesterol molecules fill space between phospholipid tails. Organelles, such as mitochondria and Golgi apparatus, are separated from 24. Bone is rigid due to calcification; cartilage is firm but elastic. Bones are the cytosol by membranes. primary support structure for the body; cartilage forms the ear, nose, larynx, 5. A flexible, changeable, three-dimensional scaffold of actin, microfilaments, and spine and helps hold bones together at the joints. intermediate filaments, and microtubules. Functions: mechanical strength; sta- 25. (a) lumen—hollow inside of an organ or tube; wall—cell layer. (b) cyto- bilize position of organelles; transport material; link cells together; movement. plasm—everything inside the cell except the nucleus; cytosol—semi-gelat- 6. (a) 2, (b) 3, (c) 1, (d) 4 inous, intracellular fluid. (c) myosin—motor protein filament; keratin— 7. serous secretions; mucous secretions structural protein fiber. 8. (a) 3, (b) 5, (c) 4, (d) 1, (e) 2 26. Apoptosis—it is a normal part of development. 9. very acidic conditions 27. (a) cell junctions: 1 (gap junctions), 2 (tight junction proteins), 4 (strength of desmosomes) (b) cell membrane: 1 (receptors), 2 (enzymes), 3 (barrier), 10. endocrine 4 (fluidity), 5 (ATP-dependent transporters) (c) cytoskeleton: 2 (microtu- 11. connective tissue (tendons that hold muscles to bones); epithelium (skin); bules direct movement), 4 (strength), 5 (ATP required for actin-myosin neural tissue (the brain); and muscular tissue (heart and skeletal muscles) interaction) (d) organelles: 2 (mRNA binds to ribosomes), 3 (membrane- 12. skin bounded organelles), 5 (ATP-dependent processes) (e) cilia: 2 (microtu- 13. (a) 1, (b) 1, (c) 4, (d) 3, (e) 4, (f) 4, (g) 4, (h) 1, (i) 1 bules and dynein), 4 (flexibility), 5 (ATP-dependent movement) 14. sweat glands—sweat; apocrine glands—waxy or milky secretions; sebaceous 28. The matrix can be dissolved and re-assembled. glands—a mixture of lipids Level Three Problem Solving 15. mitochondrial matrix—the internal compartment; tissue matrix—noncel- 29. Cilia sweep mucus and particles up and out of the airways. When they fail, lular material found outside cells inhaled pathogens are more likely to reach the lungs, resulting in infections, Level Two Reviewing Concepts inflammation, or cancer. The smoker’s cough removes the mucus that would normally be swept away by the cilia. 16. Anchoring junctions (skin)—allow twisting and stretching of tissue. Tight junctions (epithelia)—prevent movement of materials between cells. Gap 30. Many epithelia are vulnerable to damage and need to be replaced frequently. Cells junctions (some muscles)—allow material to pass directly from cytoplasm of undergoing frequent mitosis are more likely to develop abnormal cell division. one cell to another. 31. MMPs are enzymes that dissolve the extracellular matrix, so blocking them 17. Rough ER is where proteins are made, so pancreatic cells would have more. might inhibit tissue growth and repair. 18. Vesicles—membranous spheres. Examples: lysosomes, peroxisomes, secre- tory vesicles.

Photo Credits

CO: J. W. Shuler/Photo Researchers, Inc. 3.10c–d: Todd Derksen 3.3: Dr. J. M. Edwardson 3.13a: Ward’s Natural Science Establishment 3.5: Prof. P. Motta/Dept. of Anatomy/University, “La Sapienza,” Rome/ 3.13b–e: Robert B. Tallitsch Science Photo Library/Custom Medical Stock Photo 3.14: SPL/Photo Researchers 3.8(L): Don W. Fawcett/Photo Researchers, Inc. 3.15: Courtesy of Elizabeth A. Abel, M.D., from the Leonard C. 3.8(R): Prof. H. Wartenberg/Dr. H. Jastrow’s EM Atlas, (222.drjastrow.de). Winograd Memorial Slide Collection, Stanford University School of 3.9c: Robert B. Tallitsch Medicine. 3.10b: Robert B. Tallitsch

102 Energy and Cellular Metabolism

From Chapter 4 of Human Physiology: An Integrated Approach, Sixth Edition. Dee Unglaub Silverthorn. Copyright © 2013 by Pearson Education, Inc. All rights reserved.

103