Lodish H. - Molecular Cell Biology (5ed, Freeman, 2003) (794361), страница 65
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[See Y. I. Henis etal., 1990, J. Cell Biol. 111:1409.]5.1 • Biomembranes: Lipid Composition and Structural Organizationtificial membranes, a typical lipid molecule exchanges placeswith its neighbors in a leaflet about 107 times per second anddiffuses several micrometers per second at 37 C. These diffusion rates indicate that the viscosity of the bilayer is 100 timesas great as that of water—about the same as the viscosity ofolive oil. Even though lipids diffuse more slowly in the bilayerthan in an aqueous solvent, a membrane lipid could diffuse thelength of a typical bacterial cell (1 m) in only 1 second andthe length of an animal cell in about 20 seconds.The lateral movements of specific plasma-membrane proteins and lipids can be quantified by a technique called fluorescence recovery after photobleaching (FRAP).
With thismethod, described in Figure 5-6, the rate at which membranelipid or protein molecules move—the diffusion coefficient—can be determined, as well as the proportion of the moleculesthat are laterally mobile.The results of FRAP studies with fluorescence-labeledphospholipids have shown that, in fibroblast plasma membranes, all the phospholipids are freely mobile over distancesof about 0.5 m, but most cannot diffuse over much longerdistances.
These findings suggest that protein-rich regions ofthe plasma membrane, about 1 m in diameter, separatelipid-rich regions containing the bulk of the membranephospholipid. Phospholipids are free to diffuse within sucha region but not from one lipid-rich region to an adjacentone. Furthermore, the rate of lateral diffusion of lipids in theplasma membrane is nearly an order of magnitude slowerthan in pure phospholipid bilayers: diffusion constants of108 cm2/s and 107 cm2/s are characteristic of the plasmamembrane and a lipid bilayer, respectively. This differencesuggests that lipids may be tightly but not irreversibly boundto certain integral proteins in some membranes.153Lipid Composition Influences the PhysicalProperties of MembranesA typical cell contains myriad types of membranes, each withunique properties bestowed by its particular mix of lipidsand proteins. The data in Table 5-1 illustrate the variationin lipid composition among different biomembranes.
Severalphenomena contribute to these differences. For instance, differences between membranes in the endoplasmic reticulum(ER) and the Golgi are largely explained by the fact thatphospholipids are synthesized in the ER, whereas sphingolipids are synthesized in the Golgi. As a result, the proportion of sphingomyelin as a percentage of total membranelipid phosphorus is about six times as high in Golgi membranes as it is in ER membranes. In other cases, the translocation of membranes from one cellular compartment toanother can selectively enrich membranes in certain lipids.Differences in lipid composition may also correspond tospecialization of membrane function.
For example, theplasma membrane of absorptive epithelial cells lining the intestine exhibits two distinct regions: the apical surface facesthe lumen of the gut and is exposed to widely varying external conditions; the basolateral surface interacts with otherepithelial cells and with underlying extracellular structures(see Figure 6-5). In these polarized cells, the ratio of sphingolipid to phosphoglyceride to cholesterol in the basolateralmembrane is 0.5:1.5:1, roughly equivalent to that in theplasma membrane of a typical unpolarized cell subjected tomild stress.
In contrast, the apical membrane of intestinalcells, which is subjected to considerable stress, exhibits a1:1:1 ratio of these lipids. The relatively high concentrationof sphingolipid in this membrane may increase its stabilityTABLE 5-1 Major Lipid Components of Selected BiomembranesComposition (mol %)Source/LocationPCPE PSSMCholesterolPlasma membrane (human erythrocytes)21292126Myelin membrane (human neurons)1637133408500Endoplasmic reticulum membrane (rat)542657Golgi membrane (rat)45201313Inner mitochondrial membrane (rat)454527Outer mitochondrial membrane (rat)3446211Primary leaflet locationExoplasmicCytosolicPlasma membrane (E.
coli)PC phosphatidylcholine; PE phosphatidylethanolamine; PS phosphatidylserine; SM sphingomyelin.SOURCE: W. Dowhan and M. Bogdanov, 2002, in D. E. Vance and J. E. Vance, eds., Biochemistry of Lipids,Lipoproteins, and Membranes, Elsevier.ExoplasmicBoth154CHAPTER 5 • Biomembranes and Cell Architecturebecause of extensive hydrogen bonding by the free OOHgroup in the sphingosine moiety (see Figure 5-5).The ability of lipids to diffuse laterally in a bilayer indicatesthat it can act as a fluid. The degree of bilayer fluidity dependson the lipid composition, structure of the phospholipid hydrophobic tails, and temperature.
As already noted, van derWaals interactions and the hydrophobic effect cause the nonpolar tails of phospholipids to aggregate. Long, saturated fattyacyl chains have the greatest tendency to aggregate, packingtightly together into a gel-like state. Phospholipids with shortfatty acyl chains, which have less surface area for interaction,form more fluid bilayers.
Likewise, the kinks in unsaturatedfatty acyl chains result in their forming less stable van derWaals interactions with other lipids than do saturated chainsand hence more fluid bilayers. When a highly ordered, gel-likebilayer is heated, the increased molecular motions of the fattyacyl tails cause it to undergo a transition to a more fluid, disordered state (Figure 5-7).At usual physiologic temperatures, the hydrophobic interior of natural membranes generally has a low viscosityand a fluidlike, rather than gel-like, consistency. Cholesterol is important in maintaining the fluidity of naturalmembranes, which appears to be essential for normal cellgrowth and reproduction. As noted previously, cholesterolcannot form a sheetlike bilayer on its own. At concentrations found in natural membranes, cholesterol is interca-HeatGel-like consistencyFluidlike consistency(a)3.5 nm4.0 nmPC(b)4.6–5.6 nmPC andcholesterolSMSM andcholesterol(c)PCPE▲ FIGURE 5-8 Effect of lipid composition on bilayerthickness and curvature.
(a) A pure sphingomyelin (SM) bilayeris thicker than one formed from a phosphoglyceride such asphosphatidylcholine (PC). Cholesterol has a lipid-ordering effecton phosphoglyceride bilayers that increases their thickness butdoes not affect the thickness of the more ordered SM bilayer.(b) Phospholipids such as PC have a cylindrical shape and formmore or less flat monolayers, whereas those with smaller headgroups such as phosphatidylethanolamine (PE) have a conicalshape. (c) A bilayer enriched with PC in the exoplasmic leafletand with PE in the cytosolic face, as in many plasmamembranes, would have a natural curvature.
[Adapted fromH. Sprong et al., 2001, Nature Rev. Mol. Cell Biol. 2:504.]▲ FIGURE 5-7 Gel and fluid forms of the phospholipidbilayer. (Top) Depiction of gel-to-fluid transition. Phospholipidswith long saturated fatty acyl chains tend to assemble into ahighly ordered, gel-like bilayer in which there is little overlap ofthe nonpolar tails in the two leaflets. Heat disorders the nonpolartails and induces a transition from a gel to a fluid within atemperature range of only a few degrees. As the chains becomedisordered, the bilayer also decreases in thickness.
(Bottom)Molecular models of phospholipid monolayers in gel and fluidstates, as determined by molecular dynamics calculations.[Bottom based on H. Heller et al., 1993, J. Phys. Chem. 97:8343.]lated (inserted) among phospholipids. Cholesterol restrictsthe random movement of phospholipid head groups at theouter surfaces of the leaflets, but its effect on the movementof long phospholipid tails depends on concentration. At theusual cholesterol concentrations, the interaction of thesteroid ring with the long hydrophobic tails of phospholipids tends to immobilize these lipids and thus decreasebiomembrane fluidity.
At lower cholesterol concentrations,however, the steroid ring separates and disperses phospholipid tails, causing the inner regions of the membrane to become slightly more fluid.The lipid composition of a bilayer also influences its thickness, which in turn may play a role in localizing proteins to aparticular membrane. The results of studies on artificial membranes demonstrate that sphingomyelin associates into a5.1 • Biomembranes: Lipid Composition and Structural Organizationmore gel-like and thicker bilayer than phospholipids do (Figure 5-8a). Similarly, cholesterol and other molecules that decrease membrane fluidity increase membrane thickness.Because sphingomyelin tails are already optimally stabilized,the addition of cholesterol has no effect on the thickness of asphingomyelin bilayer.Another property dependent on the lipid compositionof a bilayer is its local curvature, which depends on the relative sizes of the polar head groups and nonpolar tails ofits constituent phospholipids.
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