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Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002.

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Biochemistry. 5th edition.

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Section 12.6Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane

Biological membranes are not rigid, static structures. On the contrary, lipids and many membrane proteins are constantly in lateral motion, a process called lateral diffusion. The rapid lateral movement of membrane proteins has been visualized by means of fluorescence microscopy through the use of the technique of fluorescence recovery after photobleaching (FRAP; Figure 12.29). First, a cell-surface component is specifically labeled with a fluorescent chromophore. A small region of the cell surface (~3 μm2) is viewed through a fluorescence microscope. The fluorescent molecules in this region are then destroyed (bleached) by a very intense light pulse from a laser. The fluorescence of this region is subsequently monitored as a function of time by using a light level sufficiently low to prevent further bleaching. If the labeled component is mobile, bleached molecules leave and unbleached molecules enter the illuminated region, which results in an increase in the fluorescence intensity. The rate of recovery of fluorescence depends on the lateral mobility of the fluorescence-labeled component, which can be expressed in terms of a diffusion coefficient, D. The average distance s traversed in time t depends on D according to the expression

Image ch12e1.jpg

Figure 12.29. Fluorescence Recovery After Photobleaching (FRAP) Technique.

Figure 12.29

Fluorescence Recovery After Photobleaching (FRAP) Technique. (A) The cell-surface fluoresces because of a labeled surface component. (B) The fluorescent molecules of a small part of the surface are bleached by an intense light pulse. (C) The fluorescence (more...)

The diffusion coefficient of lipids in a variety of membranes is about 1 μm2 s-1. Thus, a phospholipid molecule diffuses an average distance of 2 μm in 1 s. This rate means that a lipid molecule can travel from one end of a bacterium to the other in a second. The magnitude of the observed diffusion coefficient indicates that the viscosity of the membrane is about 100 times that of water, rather like that of olive oil.

In contrast, proteins vary markedly in their lateral mobility. Some proteins are nearly as mobile as lipids, whereas others are virtually immobile. For example, the photoreceptor protein rhodopsin (Section 32.3.1), a very mobile protein, has a diffusion coefficient of 0.4 μm2 s-1. The rapid movement of rhodopsin is essential for fast signaling. At the other extreme is fibronectin, a peripheral glycoprotein that interacts with the extracellular matrix. For fibronectin, D is less than 10-4 μm2 s-1. Fibronectin has a very low mobility because it is anchored to actin filaments on the inside of the plasma membrane through integrin, a transmembrane protein that links the extracellular matrix to the cytoskeleton.

12.6.1. The Fluid Mosaic Model Allows Lateral Movement but Not Rotation Through the Membrane

On the basis of the dynamic properties of proteins in membranes, S. Jonathan Singer and Garth Nicolson proposed the concept of a fluid mosaic model for the overall organization of biological membranes in 1972 (Figure 12.30). The essence of their model is that membranes are two-dimensional solutions of oriented lipids and globular proteins. The lipid bilayer has a dual role: it is both a solvent for integral membrane proteins and a permeability barrier. Membrane proteins are free to diffuse laterally in the lipid matrix unless restricted by special interactions.

Figure 12.30. Fluid Mosaic Model.

Figure 12.30

Fluid Mosaic Model. [After S. J. Singer and G. L. Nicolson. Science 175(1972):723.]

Although the lateral diffusion of membrane components can be rapid, the spontaneous rotation of lipids from one face of a membrane to the other is a very slow process. The transition of a molecule from one membrane surface to the other is called transverse diffusion or flip-flop (Figure 12.31) The flip-flop of phospholipid molecules in phosphatidyl choline vesicles has been directly measured by electron spin resonance techniques, which show that a phospholipid molecule flip-flops once in several hours. Thus, a phospholipid molecule takes about 109 times as long to flip-flop across a membrane as it takes to diffuse a distance of 50 Å in the lateral direction. The free-energy barriers to flip-flopping are even larger for protein molecules than for lipids because proteins have more extensive polar regions. In fact, the flip-flop of a protein molecule has not been observed. Hence, membrane asymmetry can be preserved for long periods.

Figure 12.31. Lipid Movement in Membranes.

Figure 12.31

Lipid Movement in Membranes. Lateral diffusion of lipids is much more rapid than transverse diffusion (flip-flop).

12.6.2. Membrane Fluidity Is Controlled by Fatty Acid Composition and Cholesterol Content

Many membrane processes, such as transport or signal transduction, depend on the fluidity of the membrane lipids, which in turn depends on the properties of fatty acid chains, which can exist in an ordered, rigid state or in a relatively disordered, fluid state. The transition from the rigid to the fluid state occurs rather abruptly as the temperature is raised above Tm, the melting temperature (Figure 12.32). This transition temperature depends on the length of the fatty acyl chains and on their degree of unsaturation (Table 12.3). The presence of saturated fatty acyl residues favors the rigid state because their straight hydrocarbon chains interact very favorably with each other. On the other hand, a cis double bond produces a bend in the hydrocarbon chain. This bend interferes with a highly ordered packing of fatty acyl chains, and so Tm is lowered (Figure 12.33). The length of the fatty acyl chain also affects the transition temperature. Long hydrocarbon chains interact more strongly than do short ones. Specifically, each additional -CH2- group makes a favorable contribution of about -0.5 kcal mol-1 (-2.1 kJ mol-1) to the free energy of interaction of two adjacent hydrocarbon chains.

Figure 12.32. The Phase-Transition, or Melting, Temperature (Tm) for a Phospholipid Membrane.

Figure 12.32

The Phase-Transition, or Melting, Temperature (Tm) for a Phospholipid Membrane. As the temperature is raised, the phospholipid membrane changes from a packed, ordered state to a more random one.

Table 12.3. The melting temperature of phosphatidyl choline containing different pairs of identical fatty acid chains.

Table 12.3

The melting temperature of phosphatidyl choline containing different pairs of identical fatty acid chains.

Figure 12.33. Packing of Fatty Acid Chains in a Membrane.

Figure 12.33

Packing of Fatty Acid Chains in a Membrane. The highly ordered packing of fatty acid chains is disrupted by the presence of cis double bonds. The space-filling models show the packing of (A) three molecules of stearate (C18, saturated) and (B) a molecule (more...)

Bacteria regulate the fluidity of their membranes by varying the number of double bonds and the length of their fatty acyl chains. For example, the ratio of saturated to unsaturated fatty acyl chains in the E. coli membrane decreases from 1.6 to 1.0 as the growth temperature is lowered from 42°C to 27°C. This decrease in the proportion of saturated residues prevents the membrane from becoming too rigid at the lower temperature.

In animals, cholesterol is the key regulator of membrane fluidity. Cholesterol contains a bulky steroid nucleus with a hydroxyl group at one end and a flexible hydrocarbon tail at the other end. Cholesterol inserts into bilayers with its long axis perpendicular to the plane of the membrane. The hydroxyl group of cholesterol forms a hydrogen bond with a carbonyl oxygen atom of a phospholipid head group, whereas the hydrocarbon tail of cholesterol is located in the nonpolar core of the bilayer. The different shape of cholesterol compared with phospholipids disrupts the regular interactions between fatty acyl chains. In addition, cholesterol appears to form specific complexes with some phospholipids. Such complexes may concentrate in specific regions within membranes. One result of these interactions is the moderation of membrane fluidity, making membranes less fluid but at the same time less subject to phase transitions.

12.6.3. All Biological Membranes Are Asymmetric

Membranes are structurally and functionally asymmetric. The outer and inner surfaces of all known biological membranes have different components and different enzymatic activities. A clear-cut example is the pump that regulates the concentration of Na+ and K+ ions in cells (Figure 12.34). This transport protein is located in the plasma membrane of nearly all cells in higher organisms. The Na+-K+ pump is oriented so that it pumps Na+ out of the cell and K+ into it. Furthermore, ATP must be on the inside of the cell to drive the pump. Ouabain, a specific inhibitor of the pump, is effective only if it is located outside.

Figure 12.34. Asymmetry of the Na+ -K+ transport system in plasma membranes.

Figure 12.34

Asymmetry of the Na+ -K+ transport system in plasma membranes. The Na+-K+ transport system pumps Na+ out of the cell and K+ into the cell.

Membrane proteins have a unique orientation because they are synthesized and inserted into the membrane in an asymmetric manner. This absolute asymmetry is preserved because membrane proteins do not rotate from one side of the membrane to the other and because membranes are always synthesized by the growth of preexisting membranes. Lipids, too, are asymmetrically distributed as a consequence of their mode of biosynthesis, but this asymmetry is usually not absolute, except for glycolipids. In the red-blood-cell membrane, sphingomyelin and phosphatidyl choline are preferentially located in the outer leaflet of the bilayer, whereas phosphatidyl ethanolamine and phosphatidyl serine are located mainly in the inner leaflet. Large amounts of cholesterol are present in both leaflets.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2002, W. H. Freeman and Company.
Bookshelf ID: NBK22534

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