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1 2 Cell membranes are gatekeepers. Cell membranes control the movement of material into and out of the cell Every cell is bordered by a plasma membrane. Just as skin covers our bodies, every cell of every living thing on earth, whether a prokaryote or a eukaryote, is enclosed by a plasma membrane, a two-layered membrane that holds the contents of a cell in place and regulates what enters and leaves the cell. Plasma membranes are thin (a stack of a thousand would be only as thick as a single hair) and flexible, and in photos or diagrams the membranes often resemble simple plastic bags, holding the cell contents in place. This image is a gross oversimplification, however. Membranes are indeed thin and flexible, but they are far from simple: a close look at a plasma membrane will reveal that its surface is filled with pores, outcroppings, channels, and complex molecules floating around within the two layers of the membrane itself (FIGURE 3-8). Why are plasma membranes such complex structures? It s because they perform several critical functions beyond simply acting as the boundary for a cell s interior contents. Cells, after all, are perpetually interacting with their external environment. They take in food and nutrients and dispose of waste products. They take in water. They build and export molecules needed elsewhere in the body. Sometimes they absorb heat from the outside environment, whereas at other times they dissipate excess heat generated by cell activities. Like the booths or checkpoints at a country s borders that control the flow of people into and out of the country, plasma membranes serve as gatekeepers that control the flow of molecules into and out of the cell. The foundation of all plasma membranes is a layer of lipid molecules all packed together. These are a special type of lipid, called phospholipids, which, as you may recall from Chapter 2, have what appear to be a head and two long tails. The head consists of a molecule of glycerol linked to a molecule containing phosphorus (FIGURE 3-9). This head region is said to be polar, because it has an electrical charge. As you may also recall from Chapter 2, water is also a polar molecule and, for this reason, other polar molecules mix easily with water. 85 Nine Cell Landmarks

2 PLASMA MEMBRANE Plasma membranes are made up of two layers that are filled with a variety of pores, molecules, and channels. Plasma membrane TEM 100,000 FUNCTIONS Holds contents of cell in place Takes in food and nutrients Builds and exports molecules Absorbs and dissipates heat Inside cell 1 Plasma membranes are the gatekeepers of the cell. Inside cell 2 FIGURE 3-8 More than just an outer layer. The plasma membrane performs several critical functions beyond simply enclosing a cell s interior contents. Molecules that can mix with water are described as hydrophilic ( water-loving ) molecules. The two tails of the phospholipid are long chains of carbon and hydrogen atoms. Because they have no electrical charge, the carbon-hydrogen chains are non-polar. And because they are non-polar, these tails do not mix with water and are said to be hydrophobic ( water-fearing ). The chemical structure of phospholipids gives them a sort of split personality: their hydrophilic head PHOSPHOLIPID BILAYER: STRUCTURE HYDROPHILIC HEAD Attracted to water Composed of a glycerol linked to phosphorus-containing molecule EXTRACELLULAR FLUID watery fluid outside cell INTRACELLULAR FLUID watery fluid inside cell Plasma membrane HYDROPHOBIC TAILS Not attracted to water Composed of carbonhydrogen chains Hydrophilic heads extend toward the intracellular and extracellular fluid, and hydrophobic tails are directed away from these watery fluids. FIGURE 3-9 Good membrane material. The phospholipid bilayer of the plasma membrane prevents fluid from leaking out of the cell. 86 CHAPTER 3 CELLS The Cell Cell Membranes Crossing the Membrane Cell Connections

3 region mixes easily with water, while their hydrophobic tail region does not mix with water. The split personality of phospholipids makes them good membrane material. Once a large number of phospholipids are packed together with all of their heads facing one way and their tails the other, we have a sheet with one side that is hydrophilic and one that is hydrophobic. In a cell s plasma membrane, two of these sheets of phospholipids are arranged so that the hydrophobic tails are all in contact with one another and the hydrophilic heads are in contact with the watery solution outside and inside the cell (see Figure 3-9). This arrangement gives us another way to describe the structure of the plasma membrane: as a phospholipid bilayer. The phospholipids are not locked in place in the plasma membrane; they just float around in their side of the bilayer. They cannot pop out of the membrane, or flop from one side to the other, because their hydrophobic tails always line up away from any watery solution. Just as similarly charged sides of two magnets push away from each other, so do the hydrophobic tails in the center of the membrane push away from and avoid coming into contact with water molecules. Because the center part of the bilayer membrane is made up of hydrophobic lipids, the solution on one side of the membrane cannot leak across into the solution on the other side. In this way, the plasma membrane forms a boundary around the cell s contents. TAKE-HOME MESSAGE 34 Every cell of every living organism is enclosed by a plasma membrane, a two-layered membrane that holds the contents of a cell in place and regulates what enters and leaves the cell Molecules embedded in the plasma membrane help it perform its functions. While the plasma membrane s phospholipid bilayer construction forms the cell s basic boundary with its environment, there is much more to a plasma membrane. Embedded within or attached to the phospholipid bilayer are different types of protein, carbohydrate, and lipid molecules (FIGURE 3-10). The proteins found in the plasma membrane enable it to carry out most of its gatekeeping functions. For every 50 to 100 phospholipids in the membrane, there is one protein molecule. Some of these proteins, called transmembrane proteins, penetrate right through the lipid bilayer, from one side to the other. Others, called surface proteins, reside primarily on the inner or outer surface of the membrane. What determines whether a protein resides on the surface or extends through the bilayer? Its tertiary structure. Remember from Chapter 2 that all the amino acids that make up each protein have side chains that differ from one another chemically. Some of these side chains are hydrophobic, others are hydrophilic, and as a protein is assembled into its final shape, these side chains can cause parts of the protein to be attracted to hydrophobic or hydrophilic regions. Because a MOLECULES WITHIN THE PLASMA MEMBRANE Extracellular fluid Hydrophilic region Hydrophobic region Carbohydrates Plasma membrane Transmembrane protein Lipid Surface proteins Intracellular fluid Hydrophobic and hydrophilic forces determine the orientation of proteins in the plasma membrane. FIGURE 3-10 Protein and carbohydrate molecules are embedded in the plasma membrane. 87 Nine Cell Landmarks

4 FUNCTION OF PLASMA MEMBRANE MOLECULES Extracellular fluid CARBOHYDRATE CHAINS Provide a fingerprint for the cell, so it can be recognized by other cells CHOLESTEROL Helps the membrane retain its flexibility REACTIONS REACTIONS Intracellular fluid RECEPTOR PROTEINS Bind to external chemicals in order to regulate processes within the cell RECOGNITION PROTEINS Provide a fingerprint for the cell, so it can be recognized by other cells TRANSPORT PROTEINS Provide a passageway for molecules to travel into and out of the cell ENZYMATIC PROTEINS Accelerate intracellular and extracellular reactions on the plasma membrane FIGURE 3-11 Plasma membrane molecules serve diverse roles. transmembrane protein has both hydrophobic and hydrophilic regions, part of the protein can be positioned in the hydrophobic region in the center of the membrane while the other part resides in the hydrophilic regions. Peripheral membrane proteins, on the other hand, reside on the membrane surface and have an entirely hydrophilic structure and so can bind only to the head regions of the phospholipids. As a consequence, they can be positioned on either the outer or the inner side of the membrane. Once membrane proteins are in place, the hydrophobic and hydrophilic forces keep them properly oriented. Because all of the components of the plasma membrane are held in the membrane in this manner, they can float around without ever popping out. There are four primary types of membrane proteins, each of which performs a different function (FIGURE 3-11). 1. Receptor proteins bind to chemicals in the cell s external environment and, by doing so, regulate certain processes within the cell. Cells in the heart, for example, have receptor proteins that bind to adrenaline, a chemical released into the bloodstream in times of extreme stress or fright.when adrenaline binds to these heart cells, the cells increase the heart s rate of contraction to pump blood through the body more quickly.you have experienced this reaction if you ve ever been startled and felt your heart start to pound. 2. Recognition proteins give each cell a fingerprint that makes it possible for the body s immune system (which 88 fights off infections) to distinguish the cells that belong inside your body from those that are invaders and need to be attacked. (Note that carbohydrates also play a role in recognition.) Recognition proteins also can help cells bind to or adhere to other cells or molecules. 3. Transport proteins are transmembrane proteins that help large and/or strongly charged molecules pass through the plasma membrane. Transport proteins come in a variety of shapes and sizes, making it possible for a wide variety of molecules to be transported. 4. Enzymatic proteins (enzymes) accelerate chemical reactions on the plasma membrane s surface (a variety of enzymatic proteins exist, with some accelerating reactions on the inside of the plasma membrane and others accelerating reactions on the outside of the plasma membrane). In addition to the various kinds of membrane proteins, two other types of molecules can be incorporated in a cell s plasma membrane. 1. Short, branched carbohydrate chains that are attached to proteins or to phospholipid heads on the outside of the cell membrane serve as part of a membrane s fingerprint, along with recognition proteins. This fingerprint allows the cell to be recognized by other cells, such as those of the immune system. 2. The plasma membrane also can contain cholesterol, a lipid that helps the membrane maintain its flexibility. It prevents the membrane from becoming too fluid or CHAPTER 3 CELLS The Cell Cell Membranes Crossing the Membrane Cell Connections

5 floppy at moderate temperatures and acts as a sort of antifreeze, preventing the membrane from becoming too rigid at freezing temperatures. The membranes of some cells are about 25% cholesterol; other plasma membranes, such as those of most bacteria and plants, have no cholesterol at all. As we ve seen, the plasma membrane is made up from several different types of molecules, like a mosaic, and many of those molecules float around, held in a proper orientation by hydrophobic and hydrophilic forces, but not always anchored in place. For these reasons, the plasma membrane is often described as a fluid mosaic. TAKE-HOME MESSAGE 3 5 The plasma membrane is a fluid mosaic of proteins, lipids, and carbohydrates. Proteins found in the plasma membrane enable it to carry out most of its gatekeeping functions. The proteins act as receptors, help molecules gain entry into and out of the cell, and catalyze reactions on the inner and outer cell surfaces. In conjunction with carbohydrates, some plasma membrane proteins identify the cell to other cells. And, in addition to the phospholipids that make up most of the plasma membrane, cholesterol is an important lipid in some membranes, influencing fluidity Faulty membranes can cause disease. With all the complexity of plasma membranes, it s not surpris ing that there are many ways in which they can malfunction. One disease that results from an improperly functioning membrane is cystic fibrosis, the single most common fatal inherited disease in the United States. At any given time, about 30,000 people in the United States have cystic fibrosis. Cystic fibrosis occurs when an individual inherits from both parents incorrect genetic instructions for producing one type of transmembrane protein. This protein occurs primarily in the membranes of cells in the lungs and digestive tract. When functioning normally, the protein serves as a passageway that allows one type of molecule chloride ions to get into and out of cells. There are more than a thousand different ways in which these genetic instructions can be defective, but in every case the result is the same: the lack of properly working chloride passageways in a cell s membrane. This defect leads to gradual accumulation of chloride ions within cells. Although it is not clear exactly how the chloride ion accumulation leads to the symptoms of cystic fibrosis, in nearly all cases two primary effects occur: an improper salt balance in the cells and a buildup of thick, sticky mucus particularly in the lungs. Normal mucus helps to protect the lungs by trapping dust and bacteria. This mucus is then moved out of the lungs (helped along by coughing). The mucus produced by someone with cystic fibrosis, however, is too thick and sticky to be moved out of the lungs, so it collects there, where it impairs lung function and increases the risk of bacterial infection. Because of the im proper cellular salt balance, one way to test for cystic fibrosis is to measure the concentration of salt in the sweat abnormally high concentrations indicate that the person has the disease. Although many high-tech treatments have been promised for the sufferers of cystic fibrosis and a great deal of research is being done on this disease, one of the most common treatments is decidedly low-tech. Parents help their children with cystic fibrosis clear the mucus out of their lungs by holding them on a steep slant, almost upside down, and vigorously patting or thumping their chest and back to shake loose the mucus in their lungs and move it to a place where they can cough it up. With careful treatment, the life expectancy of someone with cystic fibrosis can be years or longer (FIGURE 3-12). FIGURE 3-12 Moving mucus manually, or through an inhalation vest. The thick and sticky mucus produced by someone with cystic fibrosis collects in the lungs, impairing lung function and increasing the risk of bacterial infection. Thumping on the chest and back can loosen the mucus. The vest, by inflating and deflating rapidly, can have a similar effect in the course of a 20-minute session. 89 Nine Cell Landmarks

6 BETA-BLOCKERS Kidney Adrenal gland Extracellular fluid Beta-blocker chemicals Adrenaline Intracellular fluid 1 In stressful situations, the adrenal glands pump out adrenaline. 3 Adrenaline binds with betareceptors on cells, causing a faster heartbeat and increased blood pressure. Beta-blocker chemicals bind to receptors and prevent adrenaline from binding to the cell. By binding to adrenaline receptors, betablockers reduce anxiety symptoms. FIGURE 3-13 Reducing anxiety through beta-blockers. While faulty membranes can cause a disorder as serious as cystic fibrosis, pharmaceutical tinkering with cell membranes can alter cellular function in ways that have beneficial effects. For example, a group of drugs called beta-blockers is extremely effective at reducing anxiety. This effect was discovered almost accidentally the drugs were actually developed as a treatment for high blood pressure. Q Why do beta- Here s how beta-blockers work. Many cells in your body, particularly the cells of the blockers reduce heart, have receptor proteins on anxiety? their plasma membranes that can bind to adrenaline, a chemical manufactured in the adrenal glands (located atop the kidneys) that helps your body cope with stressful situations. These receptor proteins are called beta-receptors. In stressful situations, your adrenal glands pump out adrenaline (FIGURE 3-13). On reaching cells in your heart (among other locations in your body) and binding to betareceptors, the adrenaline promptly causes your heart to beat faster and more forcefully, increasing your blood pressure in the process. This reaction is fine in a short-term fight-orflight situation, but it is not healthy over the long run 90 2 Beta-receptors because the increased pressure can damage blood vessels. Depending on its severity, this reaction can also be problematic if you are giving a presentation or taking a test, or if you re in any other anxiety-producing situation. When you take a beta-blocker pill, the pill dissolves and the chemicals travel throughout your body until they encounter the beta-receptors. They bind to the receptors, hold on, and block the adrenaline from doing its job. This outcome slows your heart rate, causes a reduction in blood pressure, and can bring great relief to those suffering from the sweating and trembling associated with anxiety. TAKE-HOME MESSAGE 36 Normal cell functioning can be disrupted when cell membranes particularly the proteins embedded in them do not function properly. Such malfunctions can cause health problems, such as cystic fibrosis. But disruption of normal cell membrane function can also have beneficial, therapeutic effects, such as in the treatment of high blood pressure and anxiety. CHAPTER 3 CELLS The Cell Cell Membranes Crossing the Membrane Cell Connections

7 Membrane surfaces have a fingerprint that identifies the cell. As mentioned earlier, every cell in your body has a fingerprint made from a variety of molecules on the outside-facing surface of the cell membrane. Some of these membrane molecules vary, depending on the specific function of the cell. Others are common to all of your cells and convey to your immune system: I belong here. Cells with an improper fingerprint are recognized as foreign and are attacked by your body s defenses. Throughout our evolutionary history, this system has been tremendously valuable in helping our bodies fight infection. In some cases, however, this vigilance is a problem, like a car alarm that goes off even when you don t want it to. Suppose you receive a liver (or any other organ) transplant. Even if the donor is a close relative, the molecular fingerprint on the cells of the donated liver is not identical to your own. Consequently, your body sees the new organ as a foreign object and puts up a fight against it (FIGURE 3-14). Because your body will naturally try to reject the new organ, doctors must administer drugs that suppress your immune system. Immune suppression helps you tolerate the new liver, but, as you can imagine, it leaves you without some of the defenses to fight off other foreign invaders, such as bacteria that may cause infection. The presence or absence of certain molecular markers on plasma membranes is also responsible for a person s blood type and can lead to problems with simple blood transfusions. Q Why is it extremely unlikely that a person will catch HIV from casual contact such as shaking hands with an infected individual? The AIDS-causing virus, HIV, uses the molecular markers on plasma membranes to infect an individual s cells. These same molecular markers are also the reason that it is extremely unlikely that you can catch an HIV infection from casual contact with an infected individual, such as shaking his or her hand. The specific molecular markers involved in infection by HIV belong to a group of identifying markers called clusters of differentiation. Abbreviated as CD markers and having names such as CD1, CD2, and CD3, these marker molecules are proteins embedded in the plasma membrane that enable a cell to bind to outside molecules and, sometimes, transport them into the cell. One CD marker, called the CD4 marker, is found only on cells deep within the body and in the bloodstream, such as immune system cells and some nerve cells. It is the CD4 marker, in conjunction with another receptor, that is targeted by HIV. If the virus can find a cell with a CD4 marker, it can infect you, and because the CD4 markers never occur on the surface of your skin cells, casual contact such as touching is very unlikely Liver transplant recipient Liver is rejected. LIVER TRANSPLANT Molecular fingerprint of recipient Molecular fingerprint of donor liver Donor liver What happens when a patient receives an organ with a different molecular fingerprint from his or her own cells? Possible outcomes Liver is accepted after drugs are administered to suppress the immune system. FIGURE 3-14 Mismatched molecular fingerprints can cause difficulty in organ transplantation. 91 Nine Cell Landmarks

8 HIV TRANSMISSION Cells within the human body, and not those on the surface, have CD4 markers. HIV infects the body by binding to the CD4 markers on these cells. HIV particle CD4 markers Extracellular fluid Intracellular fluid HIV is not spread through casual contact; the virus cannot bind to skin cells because they do not have CD4 markers. FIGURE 3-15 HIV is not transmitted through casual contact. to transmit the virus (FIGURE 3-15). Even if millions of HIV particles are present on a person s hands, they just can t gain access into any of the other person s surface cells. cut might expose some of the cells in your bloodstream to the outside world, however, it is not impossible for casual transmission of HIV to occur. How does HIV get transmitted? Far and away, the most common methods of transmission involve the transfer of blood, semen, vaginal fluid, or breast milk from one individual to another. Particles of the virus are present in these fluids, as are cells already infected by the virus. As a consequence, the chief routes of transmission are from an infected mother to her child in breast milk, from an infected mother to her baby at birth, the use of contaminated needles, and unprotected sexual intercourse. Because an open sore or 92 TAKE-HOME MESSAGE 37 Every cell in your body has a fingerprint made from a variety of molecules on the outside-facing surface of the cell membrane. This molecular fingerprint is key to the function of your immune system. CHAPTER 3 CELLS Cell Membranes The Cell Crossing the Membrane Cell Connections