Biological membranes Life at the Edge
The plasma membrane Is the boundary that separates the living cell from its nonliving surroundings About 8 nm thick Controls traffic into and out of the cell The plasma membrane exhibits selective permeability It allows some substances to cross it more easily than others
Figure 7.1
Transport Across Membranes: Overcoming the Permeability Barrier
•Overcoming the permeability barrier of cell membranes is crucial to proper functioning of the cell. •Specific molecules and ions need to be selectively moved into and out of the cell or organelle . •Membranes are selectively permeable.
Definitions
•Solution – mixture of dissolved molecules in a liquid •Solute – the substance that is dissolved •Solvent – the liquid
Ion Concentrations
•The maintenance of solutes on both sides of the membrane is critical to the cell –Helps to keep the cell from rupturing •Concentration of ions on either side varies widely –Na+ and Cl- are higher outside the cell –K+ is higher inside the cell –Must balance the number of positive and negative charges, both inside and outside cell
•Ions and hydrophilic molecules cannot easily pass trough the hydrophobic membrane •Small and hydrophobic molecules can •Must know the list to the left
Cells and Transport Processes
Cells and cellular compartments - accumulate a variety of substances concentrations -very different from those of the surroundings substances that move across membranes - dissolved gases, ions, and small organic molecules; solutes
Transport is central to cell function
A central aspect of cell function - selective transport movement of ions or small organic molecules (metabolites)
Cellular membranes are fluid mosaics of lipids and proteins
Phospholipids Are the most abundant lipid in the plasma membrane Are amphipathic, containing both hydrophobic and hydrophilic regions For those who forgot…
HYDROPHOBIC SUBSTANCE cannot be dissolved in water because they do not have affinity to water. Example is oil
HYDROPHILIC SUBSTANCE can be dissolved in water because they have affinity to it. How are phospholipids and proteins arranged in the membranes of the cell?
• The fluid mosaic model of membrane structure – States that a membrane is a fluid structure with a “mosaic” of various proteins embedded in it – Or attached to a double layer of phospholipids Membrane Models: Scientific Inquiry
Membranes have been chemically analyzed And found to be composed of proteins and lipids Scientists studying the plasma membrane Reasoned that it must be a phospholipid bilayer This bilayer of molecules exists as stable boundary between two aqueous compartments
WATER Hydrophilic head Hydrophobic tail
WATER The Davson-Danielli sandwich model of membrane structure
Stated that the membrane was made up of a phospholipid bilayer sandwiched between two protein layers
Was supported by electron microscope pictures of membranes
However, there were 2 problems 1. generalization that all membranes of the cell are identical was challenged Plasma membrane is 7/8 nm thick and has three layered structure, and inner mitochondrial membrane is 6 nm thick and looks like a row of beads 2. placement of the proteins since membrane proteins are not very soluble in water Membrane proteins have hydrophobic and hydrophilic regions. If placed on the surface, hydrophobic parts would be in an aqueous environment… In 1972, Singer and Nicolson Proposed that membrane proteins are dispersed and individually inserted into the phospholipid bilayer Only their hydrophilic regions protrude far enough from the bilayer to be exposed to water According to this, the membrane is a mosaic of protein molecules bobbing in a fluid bilayer of phospholipids Hydrophilic region of protein
Phospholipid bilayer
Hydrophobic region of protein The Fluidity of Membranes
Membranes are not static sheets of molecules ! Held together by hydrophobic interactions which are weaker than covalent bonds Most of the lipids and some of the proteins can drift about laterally That is in the plane of the membrane Movement is rapid However, proteins are larger than lipids and they move slower The Fluidity of Membranes
Membrane remains fluid as temperature decreases Phospholipids settle into closely packed arrangement and the membrane solidifies The solidification temperature depends on the types of lipids it is made of The membrane remains fluid at lower temperatures if it is rich in phospholipids with unsaturated hydrocarbon tails Those hydrocarbons have kinks in the tails where the double bonds are located so they cannot pack closely as saturated hydrocarbons
The type of hydrocarbon tails in phospholipids Affects the fluidity of the plasma membrane
Fluid Viscous
Unsaturated hydrocarbon Saturated hydro- tails with kinks Carbon tails
(b) Membrane fluidity The Fluidity of Membranes Phospholipids in the plasma membrane Can move within the bilayer
Lateral movement Flip-flop (~107 times per second) (~ once per month)
(a) Movement of phospholipids Lateral movement Within the same membrane surface Fast process Flip-flop Or transverse diffusion From one membrane surface to another Slow process The Fluidity of Membranes
The membranes must be fluid to work properly Fluid as salad oil When solid it changes its permeability and enzymatic proteins in the membrane become inactive
Solutes Cross Membranes
Simple Diffusion, Facilitated Diffusion, and Active Transport
•Three quite different mechanisms are involved in moving solutes across membranes •A few molecules cross membranes by simple diffusion, the direct unaided movement dictated by differences in concentration of the solute on the two sides of the membrane •However, most solutes cannot cross the membrane this way
The Role of Membrane Carbohydrates in Cell-Cell Recognition
Cell-cell recognition Is a cell’s ability to distinguish one type of neighboring cell from another Important for organisms functioning Basis for the rejection of foreign cells by immune system
The way cells recognize other cells is by binding to surface molecules Usually carbohydrates Membrane carbohydrates Interact with the surface molecules of other cells, facilitating cell-cell recognition Usually short Some are covalently bonded to lipids forming molecules called glycolipids Most of them are bonded to proteins forming glycoproteins Synthesis and Sidedness of Membranes
Membranes have distinct inside and outside faces This affects the movement of proteins synthesized in the endomembrane system
Membrane proteins and lipids
1 •Synthesis of membrane proteins and Transmembrane glycoproteins lipids in the ER. Carbohydrates are ER added to the proteins making them Secretory protein glycoproteins
Glycolipid •Inside Golgi they undergo
Golgi 2 carbohydrate modifications becoming apparatus glycolipids
Vesicle •Proteins are transported in vesicles to the plasma membrane •The vesicles fuse with the membrane
3 releasing secretory proteins form the Plasma membrane: cell Cytoplasmic face 4 Extracellular face Transmembrane Secreted glycoprotein protein
Membrane glycolipid Membrane structure results in selective permeability
A cell must exchange materials with its surroundings, a process controlled by the plasma membrane A steady traffic of small molecules and ions moves across the membrane in both directions Sugars, amino acids and other nutrients enter the cell while waste products leave the cell The cell takes in oxygen for cellular respiration and expels CO2 It also regulates concentration of inorganic ions The Permeability of the Lipid Bilayer
Hydrophobic molecules Are lipid soluble and can pass through the membrane rapidly Examples are oxygen, hydrocarbons and CO2 Polar molecules Do not cross the membrane rapidly Examples are glucose and other sugars, water Charged atom or molecule and its surrounding shell of water penetrate the membrane even more difficult Transport Proteins
Transport proteins Allow passage of hydrophilic substances across the membrane Some of them act as channel proteins where they have hydrophilic channel that certain molecules use as a tunnel Others act as carrier proteins which hold onto their passengers and change shape in a way that shuttles them across the membrane In both cases the transport protein is specific for the substance it translocates Active transport
In other cases, transport proteins move solutes against the concentration gradient; this is called active transport. Active transport requires energy such as that released by the hydrolysis of ATP or by the simultaneous transport of another solute down an energy gradient.
Concentration gradient or Electrochemical Potential
The movement of a molecule that has no net charge is determined by its concentration gradient Simple or facilitated diffusion involve exergonic movement “down” the concentration gradient (negative ΔG) Active transport involves endergonic movement “up” the concentration gradient (positive ΔG)
The electrochemical potential
The movement of an ion is determined by its electrochemical potential the combined effect of its concentration gradient and the charge gradient across the membrane The active transport of ions across a membrane creates a charge gradient or membrane potential (Vm)
Active transport of ions
Most cells have an excess of negatively charged solutes inside the cell This charge difference favors the inward movement of cations such as Na+ and outward movement of anions such as Cl– In all organisms, active transport of ions across the plasma membrane results in asymmetric distribution of ions inside and outside the cell
Functions of active transport
Active transport couples endergonic transport to an exergonic process, usually ATP hydrolysis •Active transport performs three important cellular functions -Uptake of essential nutrients -Removal of wastes -Maintenance of nonequilibrium concentrations of certain ions
Direct active transport
accumulation of solute molecules on one side of the membrane is coupled directly to an exergonic chemical reaction This is usually hydrolysis of ATP •Transport proteins driven by ATP hydrolysis are called transport ATPases or ATPase pumps
Indirect active transport
Indirect active transport depends on the simultaneous transport of two solutes. •Favorable movement of one solute down its gradient - drives the unfavorable movement of the other up its gradient. •symport or an antiport, depending on whether the two molecules are transported in the same or different directions.
Direct Active Transport Depends on Four Types of Transport ATPases Four types of transport ATPases have been identified -P-type -V-type -F-type -ABC-type •They differ in structure, mechanism, location, and roles
P-type ATPases
members of a large family reversibly phosphorylated by ATP on a specific aspartic acid residue 8-10 transmembrane segments in a single polypeptide crosses the membrane multiple times 5 subfamilies (P1-P5)
V-type ATPases
pump protons into organelles vacuoles, vesicles, lysosomes, endosomes, and the Golgi complex two multisubunit components: integral component embedded in the membrane peripheral component that juts out from the membrane surface
F-type ATPases
found in bacteria, mitochondria and chloroplasts They transport protons and have two components: –a transmembrane pore (Fo) and –a peripheral membrane component (F1) that contains the ATP binding site. •Both are multisubunit components
ABC-type ATPases
(ATP binding cassette) transporters cassette describes the catalytic domain that binds ATP as part of the transport process comprise a very large family of transport proteins found in all organisms
Medical significance of ABC-type ATPases
some of them pump antibiotics or drugs out of cells, rendering the cell resistant to the drug
Some human tumors are resistant to drugs that normally inhibit growth of tumors resistant cells have high concentrations of an ABC transporter called MDR (multidrug resistance) transport protein
MDR transport protein
pumps hydrophobic drugs out of cells reducing the cytoplasmic concentration and hence their effectiveness transports a wide range of chemically dissimilar drugs
Indirect Active Transport Is Driven by Ion Gradients
not powered by ATP hydrolysis inward transport of molecules up their electrochemical gradients - coupled to and driven by simultaneous inward movement of Na+ (animals) or protons (plant, fungi, bacteria) down their gradients
Summary Structure of plasma membrane Transport across the membrane Fluid mosaic model Fluidity Crossing membranes Active transport Transport ATPases
Simple Diffusion
Unassisted Movement Down the Gradient movement of a solute from high to lower concentration only possible for gases, nonpolar molecules, or small polar molecules
Oxygen and the function of erythrocytes
Oxygen gas transfers the lipid bilayer readily by simple diffusion Erythrocytes take up oxygen in the lungs, where oxygen concentration is high release it in the body tissues, where oxygen concentration is low
Diffusion Always Moves Solutes Toward Equilibrium
tends to create a random solution in which the concentration is the same everywhere Solutes will move toward regions of lower concentration until the concentrations are equal
Thus diffusion is always movement toward equilibrium !!!!
Osmosis
Diffusion of Water Across a Selectively Permeable Membrane
Water molecules are polar and so are not affected by the membrane potential Water concentration is not appreciably different on opposite sides of a membrane
Osmosis
If two solutions are separated by a selectively permeable membrane, permeable to the water but not the solutes, the water will move toward the region of higher solute concentration. Osmosis For most cells, water tends to move inward
Water Balance of Cells Without Walls
Tonicity Is the ability of a solution to cause a cell to gain or lose water Has a great impact on cells without walls Depends in part on its concentration of solutes that cannot cross the membrane relative to that in the cell itself.
If a solution is isotonic The concentration of solutes is the same as it is inside the cell There will be no net movement of water
Isotonic solution
Animal cell. An H2O H2O animal cell fares best in an isotonic environ- ment unless it has special adaptations to offset the osmotic uptake or loss of water. Normal
If a solution is hypertonic The concentration of solutes is greater than it is inside the cell The cell will lose water
Hypertonic solution
H2O
Shriveled
If a solution is hypotonic The concentration of solutes is less than it is inside the cell The cell will gain water
Hypotonic solution
H2O
Lysed
A cell without rigid walls can tolerate neither excessive uptake or excessive loss of water This is automatically solved if a cell lives in isotonic surrounding Animals and other organisms without rigid cell walls living in hypertonic or hypotonic environment must have special adaptations for osmoregulation Control of water balance Water Balance of Cells with Walls
Cell walls Help maintain water balance Example: plant cell This cell swells as water enters by osmosis The elastic wall will expand only so much before it exters back pressure on the cell that opposes further water uptake At this point, the cell is turgid
If a plant cell is turgid It is in a hypotonic environment It is very firm, a healthy state in most plants
Plant cell. Plant cells are turgid (firm) and generally healthiest in H2O a hypotonic environ- ment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell.
Turgid (normal)
If a plant cell is flaccid It is in an isotonic or hypertonic environment There is not tendency for water to enter
H O H2O 2
Flaccid
A wall is of no advantage if the cell is immersed in hypertonic environment Plant cell will lose water to its surroundings and shrink Plasma membrane pulls away from the wall Plasmolysis H O Causing plant to wilt and can be lethal 2
Plasmolyzed
Solute Size
lipid bilayers are more permeable to small molecules
without a transporter even these small molecules move more slowly than in the absence of a membrane
Solute Polarity
Lipid bilayers are more permeable to nonpolar substances than to polar ones Nonpolar substances dissolve readily into the hydrophobic region of the bilayer Large nonpolar molecules such as estrogen and testosterone cross membranes easily, despite their large size
Polarity of a solute can be measured by the ratio of its solubility in an organic solvent to its solubility in water This is called the partition coefficient In general, the more nonpolar (hydrophobic) a substance is, the higher the partition coefficient is.
Solute Charge and relevance to cell function
The relative impermeability of polar substances, especially ions, is due to their association with water molecules The molecules of water form a shell of hydration around polar substances In order for these substances to move into a membrane, the water molecules must be removed, which requires energy
Every cell must maintain an electrochemical potential across its plasma membrane in order to function. In most cases this potential is a gradient of either sodium ions (animal cells) or protons (other cells). Membranes must still be able to allow ions to cross the bilayer in a controlled manner.
Facilitated Diffusion
Protein-Mediated Movement Down the Gradient In facilitated diffusion Transport proteins speed the movement of molecules across the plasma membrane Most transport proteins are very specific They transport only particular substances but not others
Transport proteins
•Transport proteins assist most solute across membranes. •These integral membrane proteins recognize the substances to be transported with great specificity. •Some move solutes to regions of lower concentration; this facilitated diffusion (or passive transport) uses no energy. Membrane Proteins and Their Functions A membrane Is a collage of different proteins embedded in the fluid matrix of the lipid bilayer
Fibers of extracellular matrix (ECM) Glycoprotein
Carbohydrate
Glycolipid EXTRACELLULAR SIDE OF MEMBRANE
Microfilaments of cytoskeleton Cholesterol Peripheral Integral CYTOPLASMIC SIDE protein protein OF MEMBRANE Figure 7.7 Membrane Proteins and Their Functions
Example red blood cells More than 50 types of proteins have been found in the plasma membrane of RBC Phospholipids form the main fabric of the membrane Proteins determine most of the membrane functions Different types of cells contain different sets of membrane proteins Integral proteins Penetrate the hydrophobic core of the lipid bilayer Are often transmembrane proteins, completely spanning the membrane Usually α helical proteins
EXTRACELLULAR SIDE N-terminus
C-terminus CYTOPLASMIC a Helix SIDE Peripheral proteins Are appendages loosely bound to the surface of the membrane Not embedded in the lipid bilayer An overview of six major functions of membrane proteins
(a) Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy ssource to actively pump substances across the membrane. ATP
(b) Enzymatic activity. A protein built into the membrane Enzymes may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway.
(c) Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape Signal of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell.
Figure 7.9 Receptor (d) Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells.
Glyco- protein
(e) Intercellular joining. Membrane proteins of adjacent cells may hook together in various kinds of junctions, such as gap junctions or tight junctions (see Figure 6.31).
(f) Attachment to the cytoskeleton and extracellular matrix (ECM). Microfilaments or other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes (see Figure 6.29).
Figure 7.9
Channel proteins Facilitate Diffusion by Forming Hydrophilic Transmembrane Channels allow specific solutes to cross the membrane directly There are three types of channels: ion channels, porins, and aquaporins
EXTRACELLULAR FLUID
Channel protein Solute CYTOPLASM
(a) A channel protein (purple) has a channel through which water molecules or a specific solute can pass.
Ion Channels
Allow Rapid Passage of Specific Ions Ion channels - lined with hydrophilic atoms remarkably selective most allow passage of just one ion separate proteins needed to transport Na+, K+, Ca2+, and Cl–, etc. Selectivity - based on both binding sites involving amino acid side chains, and a size filter
Gated channels
Most ion channels are gated, meaning that they open and close in response to some stimulus -Voltage-gated channels open and close in response to changes in membrane potential -Ligand-gated channels are triggered by the binding of certain substances to the channel protein -Mechano-sensitive channels respond to mechanical forces acting on the membrane
Porins
Transmembrane Proteins That Allow Rapid Passage of Various Solutes Pores on outer membranes of bacteria, mitochondria and chloroplasts are larger and less specific than ion channels The pores are formed by multipass transmembrane proteins called porins The transmembrane segments of porins cross the membrane as β barrels
Aquaporins
Transmembrane Channels That Allow Rapid Passage of Water
through membranes of erythrocytes and kidney cells in animals root cells and vacuolar membranes in plants. discovered only in 1992
Carrier proteins Undergo a subtle change in shape that translocates the solute-binding site across the membrane
Solute Carrier protein
(b) A carrier protein alternates between two conformations, moving a solute across the membrane as the shape of the protein changes. The protein can transport the solute in either direction, with the net movement being down the concentration gradient of the solute.
Carrier Proteins Are Analogous to Enzymes in Their Specificity and Kinetics
Carrier proteins are analogous to enzymes -Facilitated diffusion involves binding a substrate, on a specific solute binding site -The carrier protein and solute form an intermediate -After conformational change, the “product” is released (the transported solute) -Carrier proteins are regulated by external factors
Competitive inhibition of carrier proteins
Competitive inhibition of carrier proteins -in the presence of molecules or ions that are structurally related to the correct substrate
Example: transport of glucose by glucose carrier proteins inhibited by the other monosaccharides that the carrier accepts (mannose and galactose)
Carrier Proteins Transport Either One or Two Solutes
When a carrier protein transports a single solute across the membrane - uniport A carrier protein that transports a single solute uniporter When two solutes are transported simultaneously, and their transport is coupled - coupled transport
Coupled transport
If the two solutes are moved across a membrane in the same direction - symport (or cotransport) If the solutes are moved in opposite directions-antiport (or countertransport) Transporters that mediate these processes are symporters and antiporters
Endocytosis/Exocytosis
For substances the cell needs to take in (endo = in) or expel (exo = out) that are too large for passive or active transport
Exocytosis
Large molecules that are manufactured in the cell are released through the cell membrane.
Endocytosis Two types: phagocytosis (“cellular eating” for solids) and pinocytosis (“cellular drinking” for fluids)
Receptor mediated Endocytosis – ligands bind to specific receptors on cell surface
Summary 2 Simple diffusion Osmosis Facilitated diffusion Channel and carrier proteins Coupled transport Endocytosis Exocytosis