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Introduction and

Peter Takizawa Department of Cell Topics for today’s lecture

• Course organization

• Why

• Cell membrane Cell Biology comprises a variety of activities that discuss basic science and disease.

Lectures Website

Cell Biology

Clinical Histology Correlations Website

!The Cell Biology course proper consists of three distinct activities: lectures, histology labs and clinical correlations. In addition, there are two electives that are associated with Cell Biology: molecular and cellular basis of disease and bench to bedside. Lectures will discuss the principles and concepts of modern cellular and molecular biology, focusing on the systems and mechanisms that allow cells to survive and perform specific functions in our bodies. The first part of the course will discuss the !systems and mechanisms that are common to most cells. The second part will discuss how the different types of cells in our bodies, utilize and modify those systems to perform specific biological functions. Histology examines the structure and functions of cells and how cells form tissues and organs. Histology places the cellular mechanisms presented in lecture into the context of cell and structure. Histology also demonstrates how the !organization of cell and tissues allows organs to perform the physiological functions. Clinical correlations introduce students to clinical topics and medical terminology and demonstrate connections between basic science and disease. These presentations by physician-scientists, who are leaders in their fields, will sometimes include patients. You will notified when a patient is present. Why study cell biology to be a physician

In order to understand how disease arises and how to treat disease, we need to learn how we work under normal conditions. You must first appreciate how something is suppose to work before determining how it is broken. To understand how we work, how our bodies function under normal conditions, we must learn how the fundamental unit of works. That unit is the cell. The cell is the fundamental unit of life.

What we mean when we say that the cell is the fundamental unit of life is that cells are the smallest unit capable of growth, replication and adapting to the environment. These principles are exhibited by the many different types of single cells !, such as and , which grow and divide on their own and respond to changes in the environment to survive. But even cells from multicellular organisms, like ourselves, can survive as individual cells and under appropriate conditions, grow and divide. This second image shows human cells growing as individual cells in culture. These are HeLa cells whose initial progenitor was taken in 1951 from Henrietta Lacks who was diagnosed with cervical cancer and had a portion of the cancer was removed and the cells cancerous cultured in petri dishes. Descendants from these cells are growing and dividing !today and are widely used in biomedical research. The fact that cells can grow and adapt to environmental changes makes them fascinating subjects of study for those interested in biology and science. But why is cell biology important for medical professionals and physicians in particular? The cell is the fundamental unit of life.

What we mean when we say that the cell is the fundamental unit of life is that cells are the smallest unit capable of growth, replication and adapting to the environment. These principles are exhibited by the many different types of single cells !organisms, such as bacteria and yeast, which grow and divide on their own and respond to changes in the environment to survive. But even cells from multicellular organisms, like ourselves, can survive as individual cells and under appropriate conditions, grow and divide. This second image shows human cells growing as individual cells in culture. These are HeLa cells whose initial progenitor was taken in 1951 from Henrietta Lacks who was diagnosed with cervical cancer and had a portion of the cancer was removed and the cells cancerous cultured in petri dishes. Descendants from these cells are growing and dividing !today and are widely used in biomedical research. The fact that cells can grow and adapt to environmental changes makes them fascinating subjects of study for those interested in biology and science. But why is cell biology important for medical professionals and physicians in particular? The cell is the fundamental unit of life.

What we mean when we say that the cell is the fundamental unit of life is that cells are the smallest unit capable of growth, replication and adapting to the environment. These principles are exhibited by the many different types of single cells !organisms, such as bacteria and yeast, which grow and divide on their own and respond to changes in the environment to survive. But even cells from multicellular organisms, like ourselves, can survive as individual cells and under appropriate conditions, grow and divide. This second image shows human cells growing as individual cells in culture. These are HeLa cells whose initial progenitor was taken in 1951 from Henrietta Lacks who was diagnosed with cervical cancer and had a portion of the cancer was removed and the cells cancerous cultured in petri dishes. Descendants from these cells are growing and dividing !today and are widely used in biomedical research. The fact that cells can grow and adapt to environmental changes makes them fascinating subjects of study for those interested in biology and science. But why is cell biology important for medical professionals and physicians in particular? The cell is the fundamental unit of life.

What we mean when we say that the cell is the fundamental unit of life is that cells are the smallest unit capable of growth, replication and adapting to the environment. These principles are exhibited by the many different types of single cells !organisms, such as bacteria and yeast, which grow and divide on their own and respond to changes in the environment to survive. But even cells from multicellular organisms, like ourselves, can survive as individual cells and under appropriate conditions, grow and divide. This second image shows human cells growing as individual cells in culture. These are HeLa cells whose initial progenitor was taken in 1951 from Henrietta Lacks who was diagnosed with cervical cancer and had a portion of the cancer was removed and the cells cancerous cultured in petri dishes. Descendants from these cells are growing and dividing !today and are widely used in biomedical research. The fact that cells can grow and adapt to environmental changes makes them fascinating subjects of study for those interested in biology and science. But why is cell biology important for medical professionals and physicians in particular? We are made entirely of cells and material produced by cells.

!We are made entirely of cells and the material that cells produce. All of the activities and properties that allow us humans to grow, proliferate and adapt to our environment are generated by the cells in our body. For example, we all need to eat to obtain . Part of that process requires that we digest our food and then process the resulting small molecules: storing them we don’t need them and releasing them when we do. It would also be helpful if we had a way of handling any toxic material that we ingest with our food. One organ plays a central role in these processes: the liver. The liver helps with and absorption of food, especially . It processes most of the nutrients we obtain !from food, storing those that aren’t needed and releasing them when they are. It also detoxifies chemicals that are harmful to our bodies. If we look for these activities in the liver by dissecting it and looking it a portion, we find a mass of material. Zooming in on that material, we see mostly cells. These cells are called hepatocytes. All the critical physiological functions that are performed !by the liver, that are essential for our survival, are performed by these cells. ! We are made entirely of cells and material produced by cells.

!We are made entirely of cells and the material that cells produce. All of the activities and properties that allow us humans to grow, proliferate and adapt to our environment are generated by the cells in our body. For example, we all need to eat to obtain nutrients. Part of that process requires that we digest our food and then process the resulting small molecules: storing them we don’t need them and releasing them when we do. It would also be helpful if we had a way of handling any toxic material that we ingest with our food. One organ plays a central role in these processes: the liver. The liver helps with digestion and absorption of food, especially lipids. It processes most of the nutrients we obtain !from food, storing those that aren’t needed and releasing them when they are. It also detoxifies chemicals that are harmful to our bodies. If we look for these activities in the liver by dissecting it and looking it a portion, we find a mass of material. Zooming in on that material, we see mostly cells. These cells are called hepatocytes. All the critical physiological functions that are performed !by the liver, that are essential for our survival, are performed by these cells. ! We are made entirely of cells and material produced by cells.

!We are made entirely of cells and the material that cells produce. All of the activities and properties that allow us humans to grow, proliferate and adapt to our environment are generated by the cells in our body. For example, we all need to eat to obtain nutrients. Part of that process requires that we digest our food and then process the resulting small molecules: storing them we don’t need them and releasing them when we do. It would also be helpful if we had a way of handling any toxic material that we ingest with our food. One organ plays a central role in these processes: the liver. The liver helps with digestion and absorption of food, especially lipids. It processes most of the nutrients we obtain !from food, storing those that aren’t needed and releasing them when they are. It also detoxifies chemicals that are harmful to our bodies. If we look for these activities in the liver by dissecting it and looking it a portion, we find a mass of material. Zooming in on that material, we see mostly cells. These cells are called hepatocytes. All the critical physiological functions that are performed !by the liver, that are essential for our survival, are performed by these cells. ! We are made entirely of cells and material produced by cells.

!We are made entirely of cells and the material that cells produce. All of the activities and properties that allow us humans to grow, proliferate and adapt to our environment are generated by the cells in our body. For example, we all need to eat to obtain nutrients. Part of that process requires that we digest our food and then process the resulting small molecules: storing them we don’t need them and releasing them when we do. It would also be helpful if we had a way of handling any toxic material that we ingest with our food. One organ plays a central role in these processes: the liver. The liver helps with digestion and absorption of food, especially lipids. It processes most of the nutrients we obtain !from food, storing those that aren’t needed and releasing them when they are. It also detoxifies chemicals that are harmful to our bodies. If we look for these activities in the liver by dissecting it and looking it a portion, we find a mass of material. Zooming in on that material, we see mostly cells. These cells are called hepatocytes. All the critical physiological functions that are performed !by the liver, that are essential for our survival, are performed by these cells. ! Disease arises when cells malfunction due to genetic mutations or environmental conditions.

Normal Steatosis

From the physician’s perspective, this means that when something goes wrong with his or her patient, when disease strikes, the cause is usually some change or failure in the cells in our body. For example, genetic mutations that prevent cells from processing triglycerides or conditions in which the body contains too many triglycerides can lead to accumulation of lipids in cells of the liver. Ultimately, the activities of the cells is reduced and the ability of the liver to perform all its essential !functions is compromised, affecting the health of the patient. On the other hand, our understanding of how these cells work allow us not only identify the causes of disease but also develop treatments for those diseases. Thus, learning how the cells in our body work allows us understand the cause and progression of disease and think of ways to treat disease. Cell membrane: defining the boundary of cell The cell membrane defines the outer limit of cells.

The cell membrane defines the border of a cell. It prevents the loss of cellular material and restricts the passage of material from the external environment. Why is it needed? and other cellular material undergo rapid due to thermal energy. Something must prevent material from diffusing away from cell. Cell are selectively permeable.

Membranes restrict passage of material based on size and charge. Large molecules, such as DNA, RNA, and , can’t diffuse freely across membranes. Even the smaller subunits of proteins, nucleic and carbohydrates can’t move across membranes. Surprisingly, membranes are even restrictive to some single atoms. Most importantly, ions cannot diffuse across membranes, not because of their size but because of their strong charge. So, what can diffuse across a membrane? Gases freely diffuse which is critical for the exchange of oxygen and CO2. NO a key signaling molecule. Some larger molecules such as can diffuse across membranes. Steroids are large but hydrophobic and are important in cell communication and signaling. Cell membranes are selectively permeable.

Proteins DNA, RNA Carbohydrates

Membranes restrict passage of material based on size and charge. Large molecules, such as DNA, RNA, protein and carbohydrates, can’t diffuse freely across membranes. Even the smaller subunits of proteins, nucleic acids and carbohydrates can’t move across membranes. Surprisingly, membranes are even restrictive to some single atoms. Most importantly, ions cannot diffuse across membranes, not because of their size but because of their strong charge. So, what can diffuse across a membrane? Gases freely diffuse which is critical for the exchange of oxygen and CO2. NO a key signaling molecule. Some larger molecules such as steroids can diffuse across membranes. Steroids are large but hydrophobic and are important in cell communication and signaling. Cell membranes are selectively permeable.

Proteins DNA, RNA Carbohydrates

Nucleotides Amino Acids Sugars

Membranes restrict passage of material based on size and charge. Large molecules, such as DNA, RNA, protein and carbohydrates, can’t diffuse freely across membranes. Even the smaller subunits of proteins, nucleic acids and carbohydrates can’t move across membranes. Surprisingly, membranes are even restrictive to some single atoms. Most importantly, ions cannot diffuse across membranes, not because of their size but because of their strong charge. So, what can diffuse across a membrane? Gases freely diffuse which is critical for the exchange of oxygen and CO2. NO a key signaling molecule. Some larger molecules such as steroids can diffuse across membranes. Steroids are large but hydrophobic and are important in cell communication and signaling. Cell membranes are selectively permeable.

Proteins DNA, RNA Carbohydrates

Nucleotides Amino Acids Sugars

Na+, K+, Ca2+, Cl-, H+, Mg2+

Membranes restrict passage of material based on size and charge. Large molecules, such as DNA, RNA, protein and carbohydrates, can’t diffuse freely across membranes. Even the smaller subunits of proteins, nucleic acids and carbohydrates can’t move across membranes. Surprisingly, membranes are even restrictive to some single atoms. Most importantly, ions cannot diffuse across membranes, not because of their size but because of their strong charge. So, what can diffuse across a membrane? Gases freely diffuse which is critical for the exchange of oxygen and CO2. NO a key signaling molecule. Some larger molecules such as steroids can diffuse across membranes. Steroids are large but hydrophobic and are important in cell communication and signaling. Cell membranes are selectively permeable.

Proteins DNA, RNA Carbohydrates

Nucleotides Amino Acids Sugars

Na+, K+, Ca2+, Cl-, H+, Mg2+

O2, CO2, NO Steroids

Membranes restrict passage of material based on size and charge. Large molecules, such as DNA, RNA, protein and carbohydrates, can’t diffuse freely across membranes. Even the smaller subunits of proteins, nucleic acids and carbohydrates can’t move across membranes. Surprisingly, membranes are even restrictive to some single atoms. Most importantly, ions cannot diffuse across membranes, not because of their size but because of their strong charge. So, what can diffuse across a membrane? Gases freely diffuse which is critical for the exchange of oxygen and CO2. NO a key signaling molecule. Some larger molecules such as steroids can diffuse across membranes. Steroids are large but hydrophobic and are important in cell communication and signaling. Membranes contain hydrophilic outer surfaces and a hydrophobic core.

Water

Water

What makes membranes an effective barrier to prevent diffusion of proteins and ions is their structure? Membranes consist of a bilayer of . The layers of phospholipids are arranged into an outer leaflet that faces the external environment and an inner leaflet that faces the inside of the cell. Membranes have two key chemical properties. The outer surfaces is charged and is soluble in water. All cells exist in aqueous environments and must interact readily with water. The central core of membranes, in contrast, is hydrophobic or repels water. The hydrophobic core is what prevents the diffusion of charge molecules and ions. The ability of phospholipids to pack together tightly is what restricts the diffusion of larger !molecules. One key feature of phospholipids is that in water, their most stable conformation is to form a vesicle that encloses water. This resembles a cell. Phospholipids contain a hydrophilic head group and hydrophobic tail.

+ CH2 N (CH3)3 CH2 Hydrophilic O head group Phosphate O P O O Glycerol CH2 CH2 CH2 O O C O C O 1 2 CH2 CH2 CH2 CH2

CH2 CH2

Hydrocarbon Tail CH2 CH2

CH2 CH2 Hydrophobic CH2 CH2 CH2 CH2 tails Hydrocarbon Tail CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

The cartoon illustrates the general structure of a that composes membranes. There are two important chemical and structural features of phospholipids. The polar head group makes phospholipids soluble in water. The long hydrophobic tails allows phospholipids to self-assemble into bilayers to form membranes. The hydrophobic tails are composed of long chains of hydrocarbons. If the carbons are all linked by single bonds, then the tail is called saturated and tends to be more straight. Saturated lipids pack more closely together. A double-bond introduces a kink in the tail and prevents lipids from packing as closely together as in saturated lipids. Lipids with a double bond are called unsaturated. Biological !membranes contain a mix of saturated and unsaturated lipids as a membrane with all saturated lipids would be a solid at physiological temperature. Phospholipids can have a variety of head groups.

OH NH3 CH2 CH2 H C OH + CH2 N (CH3)3 CH2 CH2 CH2 OH OH O Ethanolamine Glycerol O P O O

CH2 CH2 CH2

O O CH3

C O C O H3C N CH3 NH3 O CH2 CH2 CH2 HC C O CH2 CH2 CH2 CH2

CH2 CH2 OH OH

CH2 CH2 Choline Serine CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2 OH H OH H CH2 CH2 2- H OH H OPO3 CH2 CH2 H HO H HO OH H OH H CH2 CH2 HO H HO H 2- CH2 CH2 H OH H OPO3

CH2 CH2

CH2 CH2 Inositol Inositol 4,5-biphosphate

CH2 CH2

CH2 CH2

One intriguing feature of phospholipids is that they can have a variety of chemically distinct head groups, a few of which are shown here. If the cell membrane merely forms a diffusion barrier, why would phospholipids need different head groups? As we’ll see the cell membrane does more than restrict the diffusion of material. It also plays a critical role in reactions. To perform these additional functions it needs proteins. Some proteins can differentiate between these head groups and cell membrane can recruit specific proteins by have more or less of certain types of phospholipids. Membranes contain a mix of phospholipids and each leaflet has a different phospholipid composition.

In a typical membrane, there will be a variety of different types of phospholipids. Phospholipid composition in the cell membrane will differ between cells. In addition, the phospholipid composition will differ between the two leaflets. The outer leaflet will contain phospholipids that help cells interact with the surrounding environment and the inner leaflet will contain phospholipids that recruit proteins from the or participate in signaling pathways. Proteins add functionality to cell membrane

As I alluded to in a previous slide, the cell membrane has to do more than just function as a diffusion barrier. How do cells get essential nutrients and material across plasma membrane?

Proteins

Nucleotides Amino Acids Sugars

Na+, K+, Ca2+, Cl-, H+, Mg2+

O2, CO2, NO Steroids

The plasma membrane restricts the diffusion of a lot of different types of molecules and ions, but cells need theses molecules, amino acids, sugars, nucleotides, to grow and survive. How do cells take up this material from the external environment while preventing the diffusion of others? How do cell their surrounding environment?

Cells must also be able to sense their surrounding environment. Single-celled organisms sense the amount of nutrients in the environment to know when is a good time to grow and divide. The cells in our body must communicate with each other. That communication is mediated by small molecules that are released to the environment and then must be detected by cells. Phospholipids cannot differentiate between all of these small molecules. How do cells stay together in multicellular organisms?

Lastly, as multicellular organisms, our cells must adhere to each other to form functional units. Remember the liver with all of the hepatocytes. Those cells must stick to each other or the liver would fall apart. Phospholipids in neighboring cells cannot interact to tether cells together. How do cells stay together in multicellular organisms?

Lastly, as multicellular organisms, our cells must adhere to each other to form functional units. Remember the liver with all of the hepatocytes. Those cells must stick to each other or the liver would fall apart. Phospholipids in neighboring cells cannot interact to tether cells together. Cell membrane contains proteins for transport of materials, adhesion and detection.

Extracellular

Intracellular

All of the functions mentioned that must be performed by the cell membrane are mediated by proteins. Cell membranes contain a variety of different types of proteins. One class is integral membrane proteins. Theses proteins span the membrane at least once and can cross the membrane multiple times. These proteins have a domain that faces the external environment and a domain that faces the interior of the cell. These proteins are permanently embedded in the membrane. A second class is peripheral membrane proteins that associate with phospholipids or integral membrane proteins. These proteins form transient interactions with the membrane as changes in the structure of the proteins or the phospholipid composition of the membrane can disrupt the interaction. A third class is GPI-anchored. These proteins are covalently attached to the head domain of specific phospholipids. These proteins face the external environment. Cell membrane contains proteins for transport of materials, adhesion and detection.

Extracellular

Intracellular

All of the functions mentioned that must be performed by the cell membrane are mediated by proteins. Cell membranes contain a variety of different types of proteins. One class is integral membrane proteins. Theses proteins span the membrane at least once and can cross the membrane multiple times. These proteins have a domain that faces the external environment and a domain that faces the interior of the cell. These proteins are permanently embedded in the membrane. A second class is peripheral membrane proteins that associate with phospholipids or integral membrane proteins. These proteins form transient interactions with the membrane as changes in the structure of the proteins or the phospholipid composition of the membrane can disrupt the interaction. A third class is GPI-anchored. These proteins are covalently attached to the head domain of specific phospholipids. These proteins face the external environment. Protein channels allow passage of small molecules and ions across membranes.

Outside

Inside

Sugars Amino acids Ions

Cell membrane contains many different types of proteins. One class is channels that span both bilayers and contain a pore that allows that passage of specific molecule or ion. The opening of these pores is tightly regulated and occasionally requires energy. Receptors allow cells to sense and communicate with outside world.

Outside

Inside

A second type of protein found in the plasma membrane is receptors that allow cells to sense and respond to the external environment. Receptors interact with specific molecules and chemicals outside the cell and relay their binding state across the membrane to activate or inactivate specific cellular events. Adhesion proteins in the cell membrane hold cells together.

Adhesion proteins in neighboring cells, interact with each other to hold cells together. Adhesion proteins in the cell membrane hold cells together.

Adhesion proteins in neighboring cells, interact with each other to hold cells together. Cell membrane and ion gradients Cell membrane allows for ion gradients between and extracellular fluid.

[K+] ~ 120 mM [K+] ~ 4.5 mM -70 mV [Na+] ~ 15 mM [Na+] ~ 145 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

As I mentioned, membranes restrict the diffusion of ions and this has important biological consequences. One is that it allows cells to create ion gradients. For most cells, the concentration of sodium is significantly higher outside the cell than inside. For potassium, the reverse is true: the concentration inside the cell is higher than outside the cell. The distribution of other ions also differs between inside and outside. One consequence of this asymmetric distribution of ions is that the overall !charge inside the cell is negative compared to the outside. Cells use these ion gradients in a variety of ways. Because sodium readily flows into the cell, cells couple the movement of sodium with the uptake of key nutrients such as . This electrical potential across the membrane is critical for cell communication, in particular between where action potentials that travel down proceed by lowering this potential difference across the membrane. Membranes keep cytosolic low and inactive.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

The other important ion that membranes restrict is calcium. Cells keep the cytosolic concentration of calcium very low because calcium activates a variety of cellular enzymes. When cells need to activate those enzymes, they increase the concentration of cytosolic calcium by opening calcium channels in the cell membrane or in the membrane of internal . Cells intensively regulate cytosolic calcium because prolonged activation of some enzymes can lead to cell damage and eventually cell death. Membranes keep cytosolic calcium low and enzymes inactive.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

The other important ion that membranes restrict is calcium. Cells keep the cytosolic concentration of calcium very low because calcium activates a variety of cellular enzymes. When cells need to activate those enzymes, they increase the concentration of cytosolic calcium by opening calcium channels in the cell membrane or in the membrane of internal organelles. Cells intensively regulate cytosolic calcium because prolonged activation of some enzymes can lead to cell damage and eventually cell death. Membranes keep cytosolic calcium low and enzymes inactive.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0020 mM

[Ca2+] ~ 1.2 mM

The other important ion that membranes restrict is calcium. Cells keep the cytosolic concentration of calcium very low because calcium activates a variety of cellular enzymes. When cells need to activate those enzymes, they increase the concentration of cytosolic calcium by opening calcium channels in the cell membrane or in the membrane of internal organelles. Cells intensively regulate cytosolic calcium because prolonged activation of some enzymes can lead to cell damage and eventually cell death. Membranes keep cytosolic calcium low and enzymes inactive.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0020 mM

[Ca2+] ~ 1.2 mM

The other important ion that membranes restrict is calcium. Cells keep the cytosolic concentration of calcium very low because calcium activates a variety of cellular enzymes. When cells need to activate those enzymes, they increase the concentration of cytosolic calcium by opening calcium channels in the cell membrane or in the membrane of internal organelles. Cells intensively regulate cytosolic calcium because prolonged activation of some enzymes can lead to cell damage and eventually cell death. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0001 mM

[Ca2+] ~ 1.2 mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0200 mM

[Ca2+] ~ 1.2 mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0200 mM

[Ca2+] ~ 1.2 mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Damage to cell membrane increases cytosolic calcium and can lead to cell death.

[Ca2+] ~ .3 mM

[Ca2+] ~ .0200 mM

[Ca2+] ~ 1.2X mM

Importantly, any damage to the cell membrane allows calcium to enter the cell and activate several cellular enzymes. Consequently, cells have active processes involving the secretory pathway that allows them to repair damage to the plasma membrane. Cells that are exposed to mechanical stress, muscle and cells that line blood vessels, are especially susceptible to damage of their plasma membranes. Strengthening the cell membrane Cell membrane are flexible and extensible but prone to damage.

Lipid membranes are very flexible and extensible as illustrated in this video showing optical tweezers pulling on a portion of a cell membrane and deforming it. This property is critical for and changes in cell shape and morphology. However, the compliance of the membranes make them prone to damage after repeated, extensive deformation. Cells in and skin are subject to strong physical forces that can damage cell membranes. Cell membrane are flexible and extensible but prone to damage.

Lipid membranes are very flexible and extensible as illustrated in this video showing optical tweezers pulling on a portion of a cell membrane and deforming it. This property is critical for cell growth and changes in cell shape and morphology. However, the compliance of the membranes make them prone to damage after repeated, extensive deformation. Cells in skeletal muscle and skin are subject to strong physical forces that can damage cell membranes. provides structural support for plasma membrane.

Membrane proteins Cytoskeleton

Cell membrane

The cytoskeleton provides mechanical support to the cell membrane. filaments are the primary cytoskeletal filaments that support the cell membrane. Actin filaments can be arranged in a variety of configurations to create different shapes of the plasma membrane (see lecture on cell morphology for details). In this image, the filaments are arranged in a mesh and tethered to the plasma membrane by interactions with integral membrane proteins. This arrangement of actin filaments provides mechanical support to a large area of the plasma membrane. If the interaction between the cytoskeleton and cell membrane is disrupted, then the cell membrane is weakened and prone to damage. Disruption of the link between cytoskeleton and cell membrane causes muscular dystrophy.

Normal

Muscular Dystrophy

The importance of the cytoskeleton in supporting the cell membrane can be seen in disease such as Duchenne’s Muscular Dystrophy. In this disease, a mutation disrupts the interaction between the cell membrane of skeletal muscle cells and the actin filaments that provide structural support to plasma membrane. Consequently, the plasma membrane in these cells is prone to damage and the muscle cells are more likely to undergo cell death. This leads to progressive weakening of the muscle. Take home points...

• Cell membranes form a diffusion barrier.

• Proteins add functionality to membranes.

• Impermeability of cell membrane allows creation of ion gradients.

• Cytoskeleton provides structural support to the cell membrane.