Membrane Structure and Function PDF

7 membrane controls traffic into and out of the cell it surrounds. Like all biological membranes, the plasma membrane exhibits...

7 membrane controls traffic into and out of the cell it surrounds. Like all biological membranes, the plasma membrane exhibits selective permeability; that is, it allows some substances to cross it more easily than others. One of the earliest episodes in the evolution of life may have been the formation of a mem- brane that enclosed a solution different from the surrounding Membrane solution while still permitting the uptake of nutrients and elimination of waste products. The ability of the cell to dis- Structure criminate in its chemical exchanges with its environment is fundamental to life, and it is the plasma membrane and its component molecules that make this selectivity possible. and Function In this chapter, you will learn how cellular membranes con- trol the passage of substances. The image in Figure 7.1 shows the elegant structure of a eukaryotic plasma membrane pro- tein that plays a crucial role in nerve cell signaling. This pro- tein provides a channel for a stream of potassium ions (K⫹) to exit a nerve cell at a precise moment after nerve stimulation, restoring the cell’s ability to fire again. (The orange ball in the center represents one potassium ion moving through the channel.) In this way, the plasma membrane and its proteins not only act as an outer boundary but also enable the cell to carry out its functions. The same applies to the many varieties of internal membranes that partition the eukaryotic cell: The molecular makeup of each membrane allows compartmental- ized specialization in cells. To understand how membranes work, we’ll begin by examining their architecture. CONCEPT 7.1 Cellular membranes are fluid mosaics of lipids and proteins 䉱 Figure 7.1 How do cell membrane proteins help regulate chemical traffic? Lipids and proteins are the staple ingredients of membranes, although carbohydrates are also important. The most abun- KEY CONCEPTS dant lipids in most membranes are phospholipids. The abil- ity of phospholipids to form membranes is inherent in their 7.1 Cellular membranes are fluid mosaics of lipids molecular structure. A phospholipid is an amphipathic and proteins molecule, meaning it has both a hydrophilic region and a 7.2 Membrane structure results in selective hydrophobic region (see Figure 5.12). Other types of mem- permeability brane lipids are also amphipathic. Furthermore, most of the 7.3 Passive transport is diffusion of a substance proteins within membranes have both hydrophobic and across a membrane with no energy investment hydrophilic regions. 7.4 Active transport uses energy to move solutes against their gradients How are phospholipids and proteins arranged in the membranes of cells? In the fluid mosaic model, the mem- 7.5 Bulk transport across the plasma membrane occurs by exocytosis and endocytosis brane is a fluid structure with a “mosaic” of various proteins embedded in or attached to a double layer (bilayer) of phos- OVERVIEW pholipids. Scientists propose models as hypotheses, ways of organizing and explaining existing information. Let’s explore Life at the Edge how the fluid mosaic model was developed. The plasma membrane is the edge of life, the boundary that Membrane Models: Scientific Inquiry separates the living cell from its surroundings. A remarkable film only about 8 nm thick—it would take over 8,000 plasma Scientists began building molecular models of the membrane membranes to equal the thickness of this page—the plasma decades before membranes were first seen with the electron CHAPTER 7 Membrane Structure and Function 125 microscope (in the 1950s). In 1915, membranes isolated from red blood cells were chemically analyzed and found to be composed of lipids and proteins. Ten years later, two Dutch scientists reasoned that cell membranes must be phospho- lipid bilayers. Such a double layer of molecules could exist as a stable boundary between two aqueous compartments be- Phospholipid cause the molecular arrangement shelters the hydrophobic bilayer tails of the phospholipids from water while exposing the hy- drophilic heads to water (Figure 7.2). If a phospholipid bilayer was the main fabric of a mem- Hydrophobic regions Hydrophilic brane, where were the proteins located? Although the heads of protein regions of protein of phospholipids are hydrophilic, the surface of a pure phos- 䉱 Figure 7.3 The original fluid mosaic model for membranes. pholipid bilayer adheres less strongly to water than does the surface of a biological membrane. Given this difference, phospholipids with water in the cytosol and extracellular Hugh Davson and James Danielli suggested in 1935 that the fluid, while providing their hydrophobic parts with a non- membrane might be coated on both sides with hydrophilic aqueous environment. In this fluid mosaic model, the mem- proteins. They proposed a sandwich model: a phospholipid brane is a mosaic of protein molecules bobbing in a fluid bilayer between two layers of proteins. bilayer of phospholipids. When researchers first used electron microscopes to study A method of preparing cells for electron microscopy called cells in the 1950s, the pictures seemed to support the freeze-fracture has demonstrated visually that proteins are in- Davson-Danielli model. By the late 1960s, however, many deed embedded in the phospholipid bilayer of the mem- cell biologists recognized two problems with the model. First, brane (Figure 7.4). Freeze-fracture splits a membrane along inspection of a variety of membranes revealed that mem- the middle of the bilayer, somewhat like pulling apart a branes with different functions differ in structure and chemi- chunky peanut butter sandwich. When the membrane layers cal composition. A second, more serious problem became are viewed in the electron microscope, the interior of the apparent once membrane proteins were better characterized. Unlike proteins dissolved in the cytosol, membrane proteins are not very soluble in water because they are amphipathic. If 䉲 Figure 7.4 RESEARCH METHOD such proteins were layered on the surface of the membrane, Freeze-fracture their hydrophobic parts would be in aqueous surroundings. APPLICATION A cell membrane can be split into its two layers, reveal- Taking these observations into account, S. J. Singer and ing the structure of the membrane’s interior. G. Nicolson proposed in 1972 that membrane proteins reside TECHNIQUE A cell is frozen and fractured with a knife. The fracture in the phospholipid bilayer with their hydrophilic regions plane often follows the hydrophobic interior of a membrane, splitting protruding (Figure 7.3). This molecular arrangement would the phospholipid bilayer into two separated layers. Each membrane maximize contact of hydrophilic regions of proteins and protein goes wholly with one of the layers. Extracellular layer 䉲 Figure 7.2 Phospholipid bilayer (cross section). Proteins WATER Knife Hydrophilic head Hydrophobic Plasma membrane Cytoplasmic layer tail RESULTS These SEMs show membrane proteins (the “bumps”) in the two layers, demonstrating that proteins are embedded in the phospho- WATER lipid bilayer. MAKE CONNECTIONS Consulting Figure 5.12 (p. 76), circle the hydrophilic and hydrophobic por- tions of the enlarged phospholipids on the right. Explain what each portion contacts when the phos- Inside of extracellular layer Inside of cytoplasmic layer pholipids are in the plasma membrane. 126 UNIT TWO The Cell  Fibers of extra- cellular matrix (ECM) Glyco- Carbohydrate protein Glycolipid EXTRACELLULAR SIDE OF MEMBRANE Cholesterol Microfilaments Peripheral of cytoskeleton proteins Integral protein 䉱 Figure 7.5 Updated model of an animal cell’s CYTOPLASMIC SIDE plasma membrane (cutaway view). OF MEMBRANE bilayer appears cobblestoned, with protein particles inter- the proteins can shift about laterally—that is, in the plane of spersed in a smooth matrix, in agreement with the fluid mo- the membrane, like partygoers elbowing their way through a saic model. Some proteins remain attached to one layer or crowded room (Figure 7.6). It is quite rare, however, for a the other, like the peanut chunks in the sandwich. molecule to flip-flop transversely across the membrane, Because models are hypotheses, replacing one model of switching from one phospholipid layer to the other; to do so, membrane structure with another does not imply that the the hydrophilic part of the molecule must cross the hy- original model was worthless. The acceptance or rejection of a drophobic interior of the membrane. model depends on how well it fits observations and explains The lateral movement of phospholipids within the mem- experimental results. New findings may make a model obso- brane is rapid. Adjacent phospholipids switch positions about lete; even then, it may not be totally scrapped, but revised to 107 times per second, which means that a phospholipid can incorporate the new observations. The fluid mosaic model is travel about 2 μm—the length of many bacterial cells—in 1 continually being refined. For example, groups of proteins are second. Proteins are much larger than lipids and move more often found associated in long-lasting, specialized patches, slowly, but some membrane proteins do drift, as shown in a where they carry out common functions. The lipids them- classic experiment described in Figure 7.7, on the next page. selves appear to form defined regions as well. Also, the mem- brane may be much more packed with proteins than imagined in the classic fluid mosaic model—compare the up- dated model in Figure 7.5 with the original model in Figure 7.3. Let’s now take a closer look at membrane structure. The Fluidity of Membranes Membranes are not static sheets of molecules locked rigidly Lateral movement occurs Flip-flopping across the membrane in place. A membrane is held together primarily by hy- ~107 times per second. is rare (~ once per month). drophobic interactions, which are much weaker than cova- lent bonds (see Figure 5.20). Most of the lipids and some of 䉱 Figure 7.6 The movement of phospholipids. CHAPTER 7 Membrane Structure and Function 127  䉲 Figure 7.7 INQUIRY its permeability changes, and enzymatic proteins in the membrane may become inactive if their activity requires Do membrane proteins move? them to be able to move within the membrane. However, EXPERIMENT Larry Frye and Michael Edidin, at Johns Hopkins Univer- membranes that are too fluid cannot support protein func- sity, labeled the plasma membrane proteins of a mouse cell and a tion either. Therefore, extreme environments pose a chal- human cell with two different markers and fused the cells. Using a mi- croscope, they observed the markers on the hybrid cell. lenge for life, resulting in evolutionary adaptations that include differences in membrane lipid composition. RESULTS Membrane proteins Evolution of Differences in Membrane Lipid Composition + Mixed proteins EVOLUTION Variations in the cell membrane lipid compo- after 1 hour sitions of many species appear to be evolutionary adaptations Mouse cell Human cell Hybrid cell that maintain the appropriate membrane fluidity under spe- CONCLUSION The mixing of the mouse and human membrane pro- cific environmental conditions. For instance, fishes that live teins indicates that at least some membrane proteins move sideways in extreme cold have membranes with a high proportion of within the plane of the plasma membrane. unsaturated hydrocarbon tails, enabling their membranes to SOURCE L. D. Frye and M. Edidin, The rapid intermixing of cell surface remain fluid (see Figure 7.8a). At the other extreme, some antigens after formation of mouse-human heterokaryons, Journal of bacteria and archaea thrive at temperatures greater than 90°C Cell Science 7:319 (1970). (194°F) in thermal hot springs and geysers. Their membranes WHAT IF? Suppose the proteins did not mix in the hybrid cell, even include unusual lipids that may prevent excessive fluidity at many hours after fusion. Would you be able to conclude that proteins don’t move within the membrane? What other explanation could there be? such high temperatures. The ability to change the lipid composition of cell mem- branes in response to changing temperatures has evolved in And some membrane proteins seem to move in a highly di- organisms that live where temperatures vary. In many plants rected manner, perhaps driven along cytoskeletal fibers by that tolerate extreme cold, such as winter wheat, the percent- motor proteins connected to the membrane proteins’ cyto- age of unsaturated phospholipids increases in autumn, an ad- plasmic regions. However, many other membrane proteins justment that keeps the membranes from solidifying during seem to be held immobile by their attachment to the cy- winter. Certain bacteria and archaea can also change the pro- toskeleton or to the extracellular matrix (see Figure 7.5). portion of unsaturated phospholipids in their cell mem- A membrane remains fluid as temperature decreases until branes, depending on the temperature at which they are finally the phospholipids settle into a closely packed arrange- growing. Overall, natural selection has apparently favored or- ment and the membrane solidifies, much as bacon grease ganisms whose mix of membrane lipids ensures an appropri- forms lard when it cools. The temperature at which a mem- ate level of membrane fluidity for their environment. brane solidifies depends on the types of lipids it is made of. The membrane remains fluid to a lower temperature if it is Fluid Viscous rich in phospholipids with unsaturated hydrocarbon tails (see Figures 5.11 and 5.12). Because of kinks in the tails where double bonds are located, unsaturated hydrocarbon tails can- not pack together as closely as saturated hydrocarbon tails, and this makes the membrane more fluid (Figure 7.8a). The steroid cholesterol, which is wedged between phospho- Unsaturated hydrocarbon Saturated hydrocarbon tails lipid molecules in the plasma membranes of animal cells, has tails (kinked) prevent packing, pack together, increasing enhancing membrane fluidity. membrane viscosity. different effects on membrane fluidity at different temperatures (Figure 7.8b). At relatively high temperatures—at 37°C, the (a) Unsaturated versus saturated hydrocarbon tails. body temperature of humans, for example—cholesterol makes the membrane less fluid by restraining phospholipid move- (b) Cholesterol within the animal cell membrane. Cholesterol ment. However, because cholesterol also hinders the close pack- reduces membrane fluidity at ing of phospholipids, it lowers the temperature required for the moderate temperatures by membrane to solidify. Thus, cholesterol can be thought of as a reducing phospholipid move- ment, but at low temperatures “fluidity buffer” for the membrane, resisting changes in mem- it hinders solidification by brane fluidity that can be caused by changes in temperature. disrupting the regular packing Cholesterol of phospholipids. Membranes must be fluid to work properly; they are usu- ally about as fluid as salad oil. When a membrane solidifies, 䉱 Figure 7.8 Factors that affect membrane fluidity. 128 UNIT TWO The Cell Membrane Proteins and Their Functions (a) Transport. Left: A protein that spans the membrane may provide a Now we come to the mosaic aspect of the fluid mosaic model. hydrophilic channel across the Somewhat like a tile mosaic, a membrane is a collage of differ- membrane that is selective for a particular solute. Right: Other transport ent proteins, often clustered together in groups, embedded in proteins shuttle a substance from one the fluid matrix of the lipid bilayer (see Figure 7.5). More than side to the other by changing shape (see Figure 7.17). Some of these 50 kinds of proteins have been found so far in the plasma proteins hydrolyze ATP as an energy membrane of red blood cells, for example. Phospholipids form source to actively pump substances across the membrane. ATP the main fabric of the membrane, but proteins determine most of the membrane’s functions. Different types of cells contain (b) Enzymatic activity. A protein built into Enzymes different sets of membrane proteins, and the various mem- the membrane may be an enzyme with branes within a cell each have a unique collection of proteins. its active site exposed to substances in the adjacent solution. In some cases, Notice in Figure 7.5 that there are two major populations several enzymes in a membrane are of membrane proteins: integral proteins and peripheral pro- organized as a team that carries out teins. Integral proteins penetrate the hydrophobic interior sequential steps of a metabolic pathway. of the lipid bilayer. The majority are transmembrane proteins, which span the membrane; other integral proteins extend (c) Signal transduction. A membrane Signaling molecule only partway into the hydrophobic interior. The hydrophobic protein (receptor) may have a binding regions of an integral protein consist of one or more stretches site with a specific shape that fits the Receptor shape of a chemical messenger, such as of nonpolar amino acids (see Figure 5.16), usually coiled into a hormone. The external messenger α helices (Figure 7.9). The hydrophilic parts of the molecule (signaling molecule) may cause the are exposed to the aqueous solutions on either side of the protein to change shape, allowing it to relay the message to the inside of the membrane. Some proteins also have a hydrophilic channel cell, usually by binding to a cytoplasmic through their center that allows passage of hydrophilic sub- protein (see Figure 11.6). stances (see Figure 7.1). Peripheral proteins are not em- Signal transduction bedded in the lipid bilayer at all; they are appendages loosely (d) Cell-cell recognition. Some glyco- bound to the surface of the membrane, often to exposed parts proteins serve as identification tags that of integral proteins (see Figure 7.5). are specifically recognized by membrane proteins of other cells. This type of On the cytoplasmic side of the plasma membrane, some cell-cell binding is usually short-lived membrane proteins are held in place by attachment to the cy- compared to that shown in (e). toskeleton. And on the extracellular side, certain membrane Glyco- proteins are attached to fibers of the extracellular matrix (see protein Figure 6.30; integrins are one type of integral protein). These attachments combine to give animal cells a stronger frame- (e) Intercellular joining. Membrane work than the plasma membrane alone could provide. proteins of adjacent cells may hook Figure 7.10 gives an overview of six major functions per- together in various kinds of junctions, formed by proteins of the plasma membrane. A single cell such as gap junctions or tight junctions (see Figure 6.32). This type of binding is more long-lasting than that shown 䉳 Figure 7.9 The structure in (d). EXTRACELLULAR of a transmembrane protein. SIDE N-terminus Bacteriorhodopsin (a bacterial transport protein) has a distinct orientation in the membrane, with (f) Attachment to the cytoskeleton and its N-terminus outside the cell and extracellular matrix (ECM). its C-terminus inside. This ribbon Microfilaments or other elements of the model highlights the α-helical cytoskeleton may be noncovalently secondary structure of the bound to membrane proteins, a function hydrophobic parts, which lie mostly that helps maintain cell shape and within the hydrophobic interior of stabilizes the location of certain the membrane. The protein membrane proteins. Proteins that can includes seven transmembrane bind to ECM molecules can coordinate helices. The nonhelical hydrophilic extracellular and intracellular changes segments are in contact with the (see Figure 6.30). α helix aqueous solutions on the 䉱 Figure 7.10 Some functions of membrane proteins. In extracellular and cytoplasmic sides many cases, a single protein performs multiple tasks. C-terminus of the membrane. Some transmembrane proteins can bind to a particular ECM mol- ? ecule and, when bound, transmit a signal into the cell. Use the CYTOPLASMIC SIDE proteins shown here to explain how this might occur. CHAPTER 7 Membrane Structure and Function 129 䉲 Figure 7.11 I M PA C T The Role of Membrane Carbohydrates in Cell-Cell Recognition Cell-cell recognition, a cell’s ability to distinguish one type of Blocking HIV Entry into Cells as a Treatment neighboring cell from another, is crucial to the functioning for HIV Infections of an organism. It is important, for example, in the sorting of cells into tissues and organs in an animal embryo. It is also D espite multiple exposures to HIV, a small number of people do not develop AIDS and show no evidence of HIV-infected cells. Comparing their genes with the genes of infected individuals, re- the basis for the rejection of foreign cells by the immune sys- tem, an important line of defense in vertebrate animals (see searchers discovered that resistant individuals have an unusual form of a gene that codes for an immune cell-surface protein called CCR5. Chapter 43). Cells recognize other cells by binding to mole- Further work showed that HIV binds to a main protein receptor cules, often containing carbohydrates, on the extracellular (CD4) on an immune cell, but on most cell types, HIV also needs to surface of the plasma membrane (see Figure 7.10d). bind to CCR5 as a “co-receptor” to infect the cell (below, left). An ab- Membrane carbohydrates are usually short, branched sence of CCR5 on the cells of resistant individuals, due to the gene chains of fewer than 15 sugar units. Some are covalently alteration, prevents the virus from entering the cells (below, right). bonded to lipids, forming molecules called glycolipids. (Re- HIV call that glyco refers to the presence of carbohydrate.) How- ever, most are covalently bonded to proteins, which are thereby glycoproteins (see Figure 7.5). The carbohydrates on the extracellular side of the plasma membrane vary from species to species, among individuals of the same species, and even from one cell type to another in a single individual. The diversity of the molecules and their lo- Receptor Receptor (CD4) cation on the cell’s surface enable membrane carbohydrates (CD4) but no CCR5 Co-receptor Plasma to function as markers that distinguish one cell from another. (CCR5) membrane For example, the four human blood types designated A, B, HIV can infect a cell that has HIV cannot infect a cell lacking AB, and O reflect variation in the carbohydrate part of glyco- CCR5 on its surface, as in CCR5 on its surface, as in proteins on the surface of red blood cells. most people. resistant individuals. WHY IT MATTERS Researchers have been searching for drugs to block Synthesis and Sidedness of Membranes cell-surface receptors involved in HIV infection. The main receptor protein, CD4, performs many important functions for cells, so interfer- Membranes have distinct inside and outside faces. The two ing with it could cause dangerous side effects. Discovery of the CCR5 lipid layers may differ in specific lipid composition, and each co-receptor provided a safer target for development of drugs that mask protein has directional orientation in the membrane (see CCR5 and block HIV entry. One such drug, maraviroc (brand name Figure 7.9). Figure 7.12 shows how membrane sidedness Selzentry), was approved for treatment of HIV infection in 2007. arises: The asymmetrical arrangement of proteins, lipids, and FURTHER READING T. Kenakin, New bull’s-eyes for drugs, Scientific their associated carbohydrates in the plasma membrane is de- American 293(4):50–57 (2005). termined as the membrane is being built by the endoplasmic MAKE CONNECTIONS Study Figures 2.18 (p. 42) and 5.19 (p. 81), reticulum (ER) and Golgi apparatus. both of which show pairs of molecules binding to each other. What would you predict about CCR5 that would allow HIV to bind to it? How could a drug molecule interfere with this binding? CONCEPT CHECK 7.1 1. The carbohydrates attached to some proteins and lipids of the plasma membrane are added as the may have membrane proteins carrying out several of these membrane is made and refined in the ER and Golgi functions, and a single membrane protein may have multiple apparatus. The new membrane then forms transport functions. In this way, the membrane is a functional mosaic vesicles that travel to the cell surface. On which side as well as a structural one. of the vesicle membrane are the carbohydrates? Proteins on the surface of a cell are important in the medical 2. WHAT IF? The soil immediately around hot springs field because some proteins can help outside agents invade the is much warmer than that in neighboring regions. cell. For example, cell-surface proteins help the human immun- Two closely related species of native grasses are found, odeficiency virus (HIV) infect immune system cells, leading to one in the warmer region and one in the cooler re- acquired immune deficiency syndrome (AIDS). (You’ll read gion. If you analyzed their membrane lipid composi- more about HIV in Chapter 19.) Learning about the proteins tions, what would you expect to find? Explain. that HIV binds to on immune cells has been central to devel- For suggested answers, see Appendix A. oping a treatment for HIV infection (Figure 7.11). 130 UNIT TWO The Cell 䉲 Figure 7.12 Synthesis of membrane components and their 11 Membrane proteins and lipids are synthesized in the orientation in the membrane. The cytoplasmic (orange) face of the endoplasmic reticulum (ER). Carbohydrates (green) are added to plasma membrane differs from the extracellular (aqua) face. The latter the transmembrane proteins (purple dumbbells), making them arises from the inside face of ER, Golgi, and vesicle membranes. glycoproteins. The carbohydrate portions may then be modified. Secretory 21 Inside the Golgi apparatus, the Transmembrane protein glycoproteins undergo further carbo- glycoproteins hydrate modification, and lipids acquire Golgi carbohydrates, becoming glycolipids. apparatus 31 The glycoproteins, glycolipids, and secretory Vesicle proteins (purple spheres) are transported in ER vesicles to the plasma membrane. ER lumen 41 As vesicles fuse with the plasma membrane, the outside face of the vesicle becomes continuous with the inside (cytoplasmic) face of Glycolipid the plasma membrane. This releases the secretory proteins from the cell, a process called exocytosis, and positions the carbohydrates of membrane glycoproteins and glycolipids on the outside (extracellular) face of the plasma membrane. Plasma membrane: Cytoplasmic face Transmembrane DRAW IT Draw an integral membrane protein Extracellular face glycoprotein Secreted extending from partway through the ER membrane protein into the ER lumen. Next, draw the protein where it would be located in a series of numbered steps end- Membrane ing at the plasma membrane. Would the protein glycolipid contact the cytoplasm or the extracellular fluid? The Permeability of the Lipid Bilayer CONCEPT 7.2 Nonpolar molecules, such as hydrocarbons, carbon dioxide, Membrane structure results and oxygen, are hydrophobic and can therefore dissolve in the lipid bilayer of the membrane and cross it easily, with- in selective permeability out the aid of membrane proteins. However, the hydropho- The biological membrane is an exquisite example of a bic interior of the membrane impedes the direct passage of supramolecular structure—many molecules ordered into a ions and polar molecules, which are hydrophilic, through higher level of organization—with emergent properties be- the membrane. Polar molecules such as glucose and other yond those of the individual molecules. The remainder of this sugars pass only slowly through a lipid bilayer, and even chapter focuses on one of the most important of those proper- water, an extremely small polar molecule, does not cross ties: the ability to regulate transport across cellular boundaries, very rapidly. A charged atom or molecule and its surround- a function essential to the cell’s existence. We will see once ing shell of water (see Figure 3.7) find the hydrophobic inte- again that form fits function: The fluid mosaic model helps ex- rior of the membrane even more difficult to penetrate. plain how membranes regulate the cell’s molecular traffic. Furthermore, the lipid bilayer is only one aspect of the gate- A steady traffic of small molecules and ions moves across the keeper system responsible for the selective permeability of a plasma membrane in both directions. Consider the chemical ex- cell. Proteins built into the membrane play key roles in reg- changes between a muscle cell and the extracellular fluid that ulating transport. bathes it. Sugars, amino acids, and other nutrients enter the cell, and metabolic waste products leave it. The cell takes in O2 for Transport Proteins use in cellular respiration and expels CO2. Also, the cell regulates Cell membranes are permeable to specific ions and a variety its concentrations of inorganic ions, such as Na⫹, K⫹, Ca2⫹, and of polar molecules. These hydrophilic substances can avoid Cl⫺, by shuttling them one way or the other across the plasma contact with the lipid bilayer by passing through transport membrane. In spite of heavy traffic through them, cell mem- proteins that span the membrane. branes are selectively permeable, and substances do not cross Some transport proteins, called channel proteins, function by the barrier indiscriminately. The cell is able to take up some having a hydrophilic channel that certain molecules or atomic small molecules and ions and exclude others. Also, substances ions use as a tunnel through the membrane (see Figure 7.10a, that move through the membrane do so at different rates. left). For example, the passage of water molecules through the CHAPTER 7 Membrane Structure and Function 131 membrane in certain cells is greatly facilitated by channel pro- diffusion, the movement of molecules of any substance so teins known as aquaporins. Each aquaporin allows entry of that they spread out evenly into the available space. Each up to 3 billion (3 ⫻ 109) water molecules per second, passing molecule moves randomly, yet diffusion of a population of single file through its central channel, which fits ten at a time. molecules may be directional. To understand this process, Without aquaporins, only a tiny fraction of these water mole- let’s imagine a synthetic membrane separating pure water cules would pass through the same area of the cell membrane from a solution of a dye in water. Study Figure 7.13a care- in a second, so the channel protein brings about a tremendous fully to appreciate how diffusion would result in both solu- increase in rate. Other transport proteins, called carrier proteins, tions having equal concentrations of the dye molecules. hold onto their passengers and change shape in a way that Once that point is reached, there will be a dynamic equilib- shuttles them across the membrane (see Figure 7.10a, right). A rium, with as many dye molecules crossing the membrane transport protein is specific for the substance it translocates each second in one direction as in the other. (moves), allowing only a certain substance (or a small group We can now state a simple rule of diffusion: In the absence of related substances) to cross the membrane. For example, a of other forces, a substance will diffuse from where it is more specific carrier protein in the plasma membrane of red blood concentrated to where it is less concentrated. Put another cells transports glucose across the membrane 50,000 times way, any substance will diffuse down its concentration faster than glucose can pass through on its own. This “glucose gradient, the region along which the density of a chemical transporter” is so selective that it even rejects fructose, a struc- substance increases or decreases (in this case, decreases). No tural isomer of glucose. work must be done to make this happen; diffusion is a spon- Thus, the selective permeability of a membrane depends taneous process, needing no input of energy. Note that each on both the discriminating barrier of the lipid bilayer and the substance diffuses down its own concentration gradient, un- specific transport proteins built into the membrane. But what affected by the concentration gradients of other substances establishes the direction of traffic across a membrane? At a (Figure 7.13b). given time, what determines whether a particular substance will enter the cell or leave the cell? And what mechanisms ac- tually drive molecules across membranes? We will address Molecules of dye Membrane (cross section) these questions next as we explore two modes of membrane traffic: passive transport and active transport. WATER CONCEPT CHECK 7.2 1. Two molecules that can cross a lipid bilayer without Net diffusion Net diffusion Equilibrium help from membrane proteins are O2 and CO2. What property allows this to occur? (a) Diffusion of one solute. The membrane has pores large enough 2. Why is a transport protein needed to move water mole- for molecules of dye to pass through. Random movement of dye molecules will cause some to pass through the pores; this will hap- cules rapidly and in large quantities across a membrane? pen more often on the side with more dye molecules. The dye 3. MAKE CONNECTIONS Aquaporins exclude passage of diffuses from where it is more concentrated to where it is less con- centrated (called diffusing down a concentration gradient). This hydronium ions (H3O⫹; see pp. 52–53). Recent re- leads to a dynamic equilibrium: The solute molecules continue to search on fat metabolism has shown that some aqua- cross the membrane, but at equal rates in both directions. porins allow passage of glycerol, a three-carbon alcohol (see Figure 5.10, p. 75), as well as H2O. Since H3O⫹ is much closer in size to water than is glycerol, what do you suppose is the basis of this selectivity? For suggested answers, see Appendix A. Net diffusion Net diffusion Equilibrium CONCEPT 7.3 Net diffusion Net diffusion Equilibrium (b) Diffusion of two solutes. Solutions of two different dyes are sepa- Passive transport is diffusion rated by a membrane that is permeable to both. Each dye diffuses down its own concentration gradient. There will be a net diffusion of a substance across a membrane of the purple dye toward the left, even though the total solute concentration was initially greater on the left side. with no energy investment 䉱 Figure 7.13 The diffusion of solutes across a synthetic Molecules have a type of energy called thermal energy (heat), membrane. Each of the large arrows under the diagrams shows the due to their constant motion. One result of this motion is net diffusion of the dye molecules of that color. 132 UNIT TWO The Cell  Much of the traffic across cell membranes occurs by diffu- Lower Higher Same concentration sion. When a substance is more concentrated on one side of concentration concentration of solute of solute (sugar) of solute a membrane than on the other, there is a tendency for the substance to diffuse across the membrane down its concen- tration gradient (assuming that the membrane is permeable Sugar to that substance). One important example is the uptake of molecule oxygen by a cell performing cellular respiration. Dissolved H 2O oxygen diffuses into the cell across the plasma membrane. As long as cellular respiration consumes the O2 as it enters, dif- Selectively permeable fusion into the cell will continue because the concentration membrane gradient favors movement in that direction. The diffusion of a substance across a biological membrane is Water molecules can pass through Water molecules called passive transport because the cell does not have to ex- pores, but sugar cluster around pend energy to make it happen. The concentration gradient it- molecules cannot. sugar molecules. self represents potential energy (see Chapter 2, p. 35) and drives diffusion. Remember, however, that membranes are selectively This side has This side has permeable and therefore have different effects on the rates of fewer solute mol- more solute mol- diffusion of various molecules. In the case of water, aquaporins ecules, more free ecules, fewer free water molecules. water molecules. allow water to diffuse very rapidly across the membranes of cer- Osmosis tain cells. As we’ll see next, the movement of water across the plasma membrane has important consequences for cells. Water moves from an area of higher to lower free water concentration (lower to higher solute concentration). Effects of Osmosis on Water Balance 䉱 Figure 7.14 Osmosis. Two sugar solutions of different To see how two solutions with different solute concentrations concentrations are separated by a membrane that the solvent (water) can pass through but the solute (sugar) cannot. Water molecules move interact, picture a U-shaped glass tube with a selectively per- randomly and may cross in either direction, but overall, water diffuses meable artificial membrane separating two sugar solutions from the solution with less concentrated solute to that with more (Figure 7.14). Pores in this synthetic membrane are too small concentrated solute. This diffusion of water, or osmosis, equalizes the sugar concentrations on both sides. for sugar molecules to pass through but large enough for water WHAT IF? If an orange dye capable of passing through the mem- molecules. How does this affect the water concentration? It brane was added to the left side of the tube above, how would it be dis- seems logical that the solution with the higher concentration tributed at the end of the experiment? (See Figure 7.13.) Would the of solute would have the lower concentration of water and final solution levels in the tube be affected? that water would diffuse into it from the other side for that reason. However, for a dilute solution like most biological flu- ids, solutes do not affect the water concentration significantly. Both factors are taken into account in the concept of Instead, tight clustering of water molecules around the hydro- tonicity, the ability of a surrounding solution to cause a cell philic solute molecules makes some of the water unavailable to gain or lose water. The tonicity of a solution depends in to cross the membrane. It is the difference in free water con- part on its concentration of solutes that cannot cross the centration that is important. In the end, the effect is the same: membrane (nonpenetrating solutes) relative to that inside Water diffuses across the membrane from the region of lower the cell. If there is a higher concentration of nonpenetrating solute concentration (higher free water concentration) to that solutes in the surrounding solution, water will tend to leave of higher solute concentration (lower free water concentra- the cell, and vice versa. tion) until the solute concentrations on both sides of the If a cell without a wall, such as an animal cell, is immersed in membrane are equal. The diffusion of free water across a selec- an environment that is isotonic to the cell (iso means “same”), tively permeable membrane, whether artificial or cellular, is there will be no net movement of water across the plasma mem- called osmosis. The movement of water across cell mem- brane. Water diffuses across the membrane, but at the same rate branes and the balance of water between the cell and its envi- in both directions. In an isotonic environment, the volume of ronment are crucial to organisms. Let’s now apply to living an animal cell is stable (Figure 7.15a, on the next page). cells what we have learned about osmosis in artificial systems. Now let’s transfer the cell to a solution that is hypertonic to the cell (hyper means “more,” in this case referring to non- penetrating solutes). The cell will lose water, shrivel, and Water Balance of Cells Without Walls probably die. This is one way an increase in the salinity (salti- To explain the behavior of a cell in a solution, we must con- ness) of a lake can kill animals there; if the lake water becomes sider both solute concentration and membrane permeability. hypertonic to the animals’ cells, the cells might shrivel and CHAPTER 7 Membrane Structure and Function 133  Hypotonic solution Isotonic solution Hypertonic solution cell doesn’t burst because it is also (a) Animal cell. An equipped with a contractile vacuole, an animal cell fares best in an isotonic environ- H2O H2O H2O H2O organelle that functions as a bilge pump ment unless it has to force water out of the cell as fast as it special adaptations enters by osmosis (Figure 7.16). We will that offset the osmotic uptake or loss of examine other evolutionary adaptations water. for osmoregulation in Chapter 44. Lysed Normal Shriveled Water Balance of Cells with Walls H2O Cell wall H2O H2O H2O (b) Plant cell. Plant cells The cells of plants, prokaryotes, fungi, are turgid (firm) and and some protists are surrounded by generally healthiest in walls (see Figure 6.28). When such a cell a hypotonic environ- ment, where the is immersed in a hypotonic solution— uptake of water is bathed in rainwater, for example—the eventually balanced wall helps maintain the cell’s water bal- by the wall pushing Turgid (normal) Flaccid Plasmolyzed back on the cell. ance. Consider a plant cell. Like an ani- mal cell, the plant cell swells as water 䉱 Figure 7.15 The water balance of living cells. How living cells react to changes in the solute concentration of their environment depends on whether or not they have cell walls. enters by osmosis (Figure 7.15b). How- (a) Animal cells, such as this red blood cell, do not have cell walls. (b) Plant cells do. (Arrows ever, the relatively inelastic wall will ex- indicate net water movement after the cells were first placed in these solutions.) pand only so much before it exerts a back pressure on the cell, called turgor die. However, taking up too much water can be just as haz- pressure, that opposes further water uptake. At this point, the ardous to an animal cell as losing water. If we place the cell in cell is turgid (very firm), which is the healthy state for most a solution that is hypotonic to the cell (hypo means “less”), plant cells. Plants that are not woody, such as most house- water will enter the cell faster than it leaves, and the cell will plants, depend for mechanical support on cells kept turgid by swell and lyse (burst) like an overfilled water balloon. a surrounding hypotonic solution. If a plant’s cells and their A cell without rigid walls can tolerate neither excessive up- surroundings are isotonic, there is no net tendency for water take nor excessive loss of water. This problem of water balance to enter, and the cells become flaccid (limp). is automatically solved if such a cell lives in isotonic surround- However, a wall is of no advantage if the cell is immersed ings. Seawater is isotonic to many marine invertebrates. The in a hypertonic environment. In this case, a plant cell, like cells of most terrestrial (land-dwelling) animals are bathed in an an animal cell, will lose water to its surroundings and shrink. extracellular fluid that is isotonic to the cells. In hypertonic or As the plant cell shrivels, its plasma membrane pulls away hypotonic environments, however, organisms that lack rigid from the wall. This phenomenon, called plasmolysis, cell walls must have other adaptations for osmoregulation, causes the plant to wilt and can lead to plant death. The the control of solute concentrations and water balance. For ex- walled cells of bacteria and fungi also plasmolyze in hyper- ample, the unicellular protist Paramecium caudatum lives in tonic environments. pond water, which is hypotonic to the cell. P. caudatum has a plasma membrane that is much less permeable to water than Facilitated Diffusion: the membranes of most other cells, but this only slows the up- Passive Transport Aided by Proteins take of water, which continually enters the cell. The P. caudatum Let’s look more closely at how water and certain hydrophilic 50 μm solutes cross a membrane. As mentioned earlier, many polar Contractile vacuole molecules and ions impeded by the lipid bilayer of the mem- brane diffuse passively with the help of transport proteins that span the membrane. This phenomenon is called facilitated diffusion. Cell biologists are still trying to learn exactly how various transport proteins facilitate diffu- sion. Most transport proteins are very specific: They transport some substances but not others. As described earlier, the two types of transport proteins are channel proteins and carrier proteins. Channel proteins simply 䉱 Figure 7.16 The contractile vacuole of Paramecium caudatum. The vacuole collects fluid from a system of canals in the cytoplasm. When provide corridors that allow specific molecules or ions to cross full, the vacuole and canals contract, expelling fluid from the cell (LM). the membrane (Figure 7.17a). The hydrophilic passageways 134 UNIT TWO The Cell  down its concentration gradient. No energy input is thus re- EXTRACELLULAR FLUID quired: This is passive transport. In certain inherited diseases, specific transport systems are either defective or missing altogether. An example is cystin- (a) A channel uria, a human disease characterized by the absence of a car- protein (purple) has a channel rier protein that transports cysteine and some other amino through which acids across the membranes of kidney cells. Kidney cells nor- Channel protein Solute water molecules or a specific mally reabsorb these amino acids from the urine and return CYTOPLASM them to the blood, but an individual afflicted with cystinuria solute can pass. develops painful stones from amino acids that accumulate and crystallize in the kidneys. CONCEPT CHECK 7.3 1. How do you think a cell performing cellular respira- tion rids itself of the resulting CO2? 2. In the supermarket, produce is often sprayed with Carrier protein Solute water. Explain why this makes vegetables look crisp. 3. WHAT IF? If a Paramecium caudatum swims from a hypotonic to an isotonic environment, will its con- (b) A carrier protein alternates between two shapes, moving a solute across the membrane during the shape change. tractile vacuole become more active or less? Why? 䉱 Figure 7.17 Two types of transport proteins that carry For suggested answers, see Appendix A. out facilitated diffusion. In both cases, the protein can transport the solute in either direction, but the net movement is down the concentration gradient of the solute. CONCEPT 7.4 provided by these proteins can allow water molecules or small Active transport uses energy to ions to diffuse very quickly from one side of the membrane to move solutes against their gradients the other. Aquaporins, the water channel proteins, facilitate the Despite the help of transport proteins, facilitated diffusion is massive amounts of diffusion that occur in plant cells and in considered passive transport because the solute is moving animal cells such as red blood cells (see Figure 7.15). Certain down its concentration gradient, a process that requires no kidney cells also have a high number of aquaporins, allowing energy. Facilitated diffusion speeds transport of a solute by them to reclaim water from urine before it is excreted. If the providing efficient passage through the membrane, but it kidneys did not perform this function, you would excrete does not alter the direction of transport. Some transport pro- about 180 L of urine per day—and have to drink an equal vol- teins, however, can move solutes against their concentration ume of water! gradients, across the plasma membrane from the side where Channel proteins that transport ions are called ion chan- they are less concentrated (whether inside or outside) to the nels. Many ion channels function as gated channels, side where they are more concentrated. which open or close in response to a stimulus. For some gated channels, the stimulus is electrical. The ion channel The Need for Energy in Active Transport shown in Figure 7.1, for example, opens in response to an electrical stimulus, allowing potassium ions to leave the cell. To pump a solute across a membrane against its gradient re- Other gated channels open or close when a specific substance quires work; the cell must expend energy. Therefore, this type other than the one to be transported binds to the channel. of membrane traffic is called active transport. The trans- Both types of gated channels are important in the function- port proteins that move solutes against their concentration ing of the nervous system, as you’ll learn in Chapter 48. gradients are all carrier proteins rather than channel proteins. Carrier proteins, such as the glucose transporter men- This makes sense because when channel proteins are open, tioned earlier, seem to undergo a subtle change in shape that they merely allow solutes to diffuse down their concentra- somehow translocates the solute-binding site across the tion gradients rather than picking them up and transporting membrane (Figure 7.17b). Such a change in shape may be them against their gradients. triggered by the binding and release of the transported mol- Active transport enables a cell to maintain internal concen- ecule. Like ion channels, carrier proteins involved in facili- trations of small solutes that differ from concentrations in its tated diffusion result in the net movement of a substance environment. For example, compared with its surroundings, CHAPTER 7 Membrane Structure and Function 135  EXTRACELLULAR [Na+] high directly to the transport protein. This can induce the protein FLUID [K+] low to change its shape in a manner that translocates a solute Na+ bound to the protein across the membrane. One transport sys- Na+ tem that works this way is the sodium-potassium pump, Na+ Na+ which exchanges Na⫹ for K⫹ across the plasma membrane of Na+ animal cells (Figure 7.18). The distinction between passive [Na+] low P ATP transport and active transport is reviewed in Figure 7.19. Na+ CYTOPLASM [K+] high ADP 1 Cytoplasmic Na+ binds to 2 Na+ binding stimulates How Ion Pumps Maintain Membrane Potential the sodium-potassium pump. phosphorylation by ATP. The affinity for Na+ is high when All cells have voltages across their plasma membranes. Voltage the protein has this shape. is electrical potential energy—a separation of opposite charges. The cytoplasmic side of the membrane is negative in charge rel- ative to the extracellular side because of an unequal distribu- Na+ tion of anions and cations on the two sides. The voltage across Na+ a membrane, called a membrane potential, ranges from Na+ about ⫺50 to ⫺200 millivolts (mV). (The minus sign indicates that the inside of the cell is negative relative to the outside.) The membrane potential acts like a battery, an energy K+ source that affects the traffic of all charged substances across P the membrane. Because the inside of the cell is negative com- K+ pared with the outside, the membrane potential favors the 6 K+ is released; affinity for 3 Phosphorylation leads to Na+ is high again, and the a change in protein shape, passive transport of cations into the cell and anions out of the cycle repeats. reducing its affinity for Na+, cell. Thus, two forces drive the diffusion of ions across a mem- which is released outside. brane: a chemical force (the ion’s concentration gradient) and an electrical force (the effect of the membrane potential on K+ 䉲 Figure 7.19 Review: passive Active transport. and active transport. Some transport proteins act as pumps, moving K+ Passive transport. Substances diffuse substances across a + K+ spontaneously down their concentration membrane against their K gradients, crossing a membrane with no concentration (or elec- expenditure of energy by the cell. The rate trochemical) gradients. P of diffusion can be greatly increased Energy for this work is P i by transport proteins in the membrane. usually supplied by ATP. 5 Loss of the phosphate 4 The new shape has a high group restores the protein’s affinity for K+, which binds original shape, which has a on the extracellular side and lower affinity for K+. triggers release of the phos- phate group. 䉱 Figure 7.18 The sodium-potassium pump: a specific case of active transport. This transport system pumps ions against steep concentration gradients: Sodium ion concentration ([Na⫹]) is high outside the cell and low inside, while potassium ion concentration ([K⫹]) is low outside the cell and high inside. The pump oscillates between two shapes in a cycle that moves 3 Na⫹ out of the cell for every 2 K⫹ pumped into the cell. The two shapes have different affinities for Na⫹ and K⫹. ATP powers the shape change by transferring a phosphate group to the transport protein (phosphorylating the protein). Diffusion. Facilitated diffusion. ATP Hydrophobic Many hydrophilic molecules and substances diffuse an animal cell has a much higher concentration of potassium (at a slow rate) through membranes very small un- with the assistance of ions (K⫹) and a much lower concentration of sodium ions charged polar transport proteins, (Na⫹). The plasma membrane helps maintain these steep gra- molecules can either channel dients by pumping Na⫹ out of the cell and K⫹ into the cell. diffuse through proteins (left) or carrier the lipid bilayer. proteins (right). As in other types of cellular work, ATP supplies the energy for most active transport. One way ATP can power active For each solute in the right panel, describe its direction of movement, transport is by transferring its terminal phosphate group ? and state whether it is going with or against its concentration gradient. 136 UNIT TWO The Cell the ion’s movement). This combination of forces acting on an Cotransport: Coupled Transport ion is called the electrochemical gradient. by a Membrane Protein In the case of ions, then, we must refine our concept of pas- A single ATP-powered pump that transports a specific solute sive transport: An ion diffuses not simply down its concentration can indirectly drive the active transport of several other gradient but, more exactly, down its electrochemical gradient. solutes in a mechanism called cotransport. A substance that For example, the concentration of Na⫹ inside a resting nerve has been pumped across a membrane can do work as it moves cell is much lower than outside it. When the cell is stimulated, back across the membrane by diffusion, analogous to water gated channels open that facilitate Na⫹ diffusion. Sodium ions that has been pumped uphill and performs work as it flows then “fall” down their electrochemical gradient, driven by the back down. Another transport protein, a cotransporter sepa- concentration gradient of Na⫹ and by the attraction of these rate from the pump, can couple the “downhill” diffusion of cations to the negative side (inside) of the membrane. In this this substance to the “uphill” transport of a second substance example, both electrical and chemical contributions to the against its own concentration (or electrochemical) gradient. electrochemical gradient act in the same direction across the For example, a plant cell uses the gradient of H⫹ generated by membrane, but this is not always so. In cases where electrical its proton pumps to drive the active transport of amino acids, forces due to the membrane potential oppose the simple diffu- sugars, and several other nutrients into the cell. One transport sion of an ion down its concentration gradient, active transport protein couples the return of H⫹ to the transport of sucrose may be necessary. In Chapter 48, you’ll learn about the impor- into the cell (Figure 7.21). This protein can translocate su- tance of electrochemical gradients and membrane potentials in crose into the cell against a concentration gradient, but only the transmission of nerve impulses. if the sucrose molecule travels in the company of a hydrogen Some membrane proteins that actively transport ions con- ion. The hydrogen ion uses the transport protein as an avenue tribute to the membrane potential. An example is the sodium- to diffuse down the electrochemical gradient maintained by potassium pump. Notice in Figure 7.18 that the pump does not the proton pump. Plants use sucrose-H⫹ cotransport to load translocate Na⫹ and K⫹ one for one, but pumps three sodium sucrose produced by photosynthesis into cells in the veins of ions out of the cell for every two potassium ions it pumps into leaves. The vascular tissue of the plant can then distribute the the cell. With each “crank” of the pump, there is a net transfer sugar to nonphotosynthetic organs, such as roots. of one positive charge from the cytoplasm to the extracellular What we know about cotransport proteins in animal cells fluid, a process that stores energy as voltage. A transport protein has helped us find more effective treatments for diarrhea, a se- that generates voltage across a membrane is called an rious problem in developing countries. Normally, sodium in electrogenic pump. The sodium-potassium pump appears to waste is reabsorbed in the colon, maintaining constant levels be the major electrogenic pump of animal cells. The main elec- in the body, but diarrhea expels waste so rapidly that reab- trogenic pump of plants, fungi, and bacteria is a proton sorption is not possible, and sodium levels fall precipitously. pump, which actively transports protons (hydrogen ions, H⫹) out of the cell. The pumping of H⫹ transfers positive charge ATP from the cytoplasm to the extracellular solution (Figure 7.20). H+ – + H+ By generating voltage across membranes, electrogenic pumps help store energy that can be tapped for cellular work. One im- Proton pump H+ H+ portant use of proton gradients in the cell is for ATP synthesis during cellular respiration, as you will see in Chapter 9. Another – + H+ is a type of membrane traffic called cotransport. H+ – H+ + H+ ATP – + EXTRACELLULAR FLUID Sucrose-H+ Diffusion of H+ – + cotransporter H+ Proton pump H+ H+ H+ Sucrose – + – + H+ Sucrose – + H+ CYTOPLASM 䉱 Figure 7.21 Cotransport: active transport driven by a concentration gradient. A carrier protein, such as this sucrose-H⫹ 䉱 Figure 7.20 A proton pump. Proton pumps are electrogenic cotransporter in a plant cell, is able to use the diffusion of H⫹ down its pumps that store energy by generating voltage (charge separation) electrochemical gradient into the cell to drive the uptake of sucrose. across membranes. A proton pump translocates positive charge in the The H⫹ gradient is maintained by an ATP-driven proton pump that form of hydrogen ions. The voltage and H⫹ concentration gradient concentrates H⫹ outside the cell, thus storing potential energy that can represent a dual energy source that can drive other processes, such as be used for active transport, in this case of sucrose. Thus, ATP indirectly the uptake of nutrients. Most proton pumps are powered by ATP. provides the energy necessary for cotransport. (The cell wall is not shown.) CHAPTER 7 Membrane Structure and Function 137 To treat this life-threatening condition, patients are given a so- Endocytosis lution to drink containing high concentrations of salt (NaCl) and glucose. The solutes are taken up by sodium-glucose In endocytosis, the cell takes in biological molecules and cotransporters on the surface of intestinal cells and passed particulate matter by forming new vesicles from the plasma through the cells into the blood. This simple treatment has membrane. Although the proteins involved in the processes lowered infant mortality worldwide. are different, the events of endocytosis look like the reverse of exocytosis. A small area of the plasma membrane sinks in- CONCEPT CHECK 7.4 ward to form a pocket. As the pocket deepens, it pinches in, forming a vesicle containing material that had been outside 1. Sodium-potassium pumps help nerve cells establish a the cell. Study Figure 7.22 carefully to understand the three voltage across their plasma membranes. Do these types of endocytosis: phagocytosis (“cellular eating”), pinocy- pumps use ATP or produce ATP? Explain. tosis (“cellular drinking”), and receptor-mediated endocytosis. 2. Explain why the sodium-potassium pump in Human cells use receptor-mediated endocytosis to take in Figure 7.18 would not be considered a cotransporter. cholesterol for membrane synthesis and the synthesis of 3. MAKE CONNECTIONS Review the characteristics of the other steroids. Cholesterol travels in the blood in particles lysosome in Concept 6.4 (pp. 106–107). Given the in- called low-density lipoproteins (LDLs), each a complex of ternal environment of a lysosome, what transport lipids and a protein. LDLs bind to LDL receptors on plasma protein might you expect to see in its membrane? membranes and then enter the cells by endocytosis. (LDLs For suggested answers, see Appendix A. thus act as ligands, a term for any molecule that binds specifically to a receptor site on another molecule.) In hu- mans with familial hypercholesterolemia, an inherited disease CONCEPT 7.5 characterized by a very high level of cholesterol in the blood, LDLs cannot enter cells because the LDL receptor proteins are Bulk transport across the plasma defective or missing. Consequently, cholesterol accumulates membrane occurs by exocytosis in the blood, where it contributes to early atherosclerosis, the buildup of lipid deposits within the walls of blood vessels. and endocytosis This buildup causes the walls to bulge inward, thereby nar- Water and small solutes enter and leave the cell by diffusing rowing the vessels and impeding blood flow. through the lipid bilayer of the plasma membrane or by Vesicles not only transport substances between the cell being pumped or moved across the membrane by transport and its surroundings but also provide a mechanism for reju- proteins. However, large molecules, such as proteins and venating or remodeling the plasma membrane. Endocytosis polysaccharides, as well as larger particles, generally cross the and exocytosis occur continually in most eukaryotic cells, yet membrane in bulk by mechanisms that involve packaging in the amount of plasma membrane in a nongrowing cell re- vesicles. Like active transport, these processes require energy. mains fairly constant. Apparently, the addition of membrane by one process offsets the loss of membrane by the other. Exocytosis Energy and cellular work have figured prominently in our study of membranes. We have seen, for example, that active As we described in Chapter 6, the cell secretes certain biological transport is powered by ATP. In the next three chapters, you molecules by the fusion of vesicles with the plasma membrane; will learn more about how cells acquire chemical energy to this process is called exocytosis. A transport vesicle that has do the work of life. budded from the Golgi apparatus moves along microtubules of the cytoskeleton to the plasma membrane. When the vesicle membrane and plasma membrane come into contact, specific CONCEPT CHECK 7.5 proteins rearrange the lipid molecules of the two bilayers so 1. As a cell grows, its plasma membrane expands. Does that the two membranes fuse. The contents of the vesicle then this involve endocytosis or exocytosis? Explain. spill to the outside of t