Analysis of membrane lipids by mass spectrometry has revealed that the lipid composition of a typical eukaryotic cell membrane is much more complex than originally thought. These membranes contain a bewildering variety of perhaps 500–2000 different lipid species with even the simple plasma membrane of a red blood cell containing well over 150. While some of this complexity reflects the combinatorial variation in head groups, hydrocarbon chain lengths, and desaturation of the major phospholipid classes, some membranes also contain many structurally distinct minor lipids, at least some of which have important functions. The inositol phospholipids, for example, are present in small quantities in animal cell membranes and have crucial functions in guiding membrane traffic and in cell signaling (discussed in Chapters 13 and 15, respectively). Their local synthesis and destruction are regulated by a large number of enzymes, which create both small intracellular signaling molecules and lipid docking sites on membranes that recruit specific proteins from the cytosol, as we discuss later.
Despite their Fluidity, lipid Bilayers can Form Domains of Different compositions
Because a lipid bilayer is a two-dimensional fluid, we might expect most types of lipid molecules in it to be well mixed and randomly distributed in their own monolayer. The van der Waals attractive forces between neighboring hydrocarbon tails are not selective enough to hold groups of phospholipid molecules together. With certain lipid mixtures in artificial bilayers, however, one can observe phase segregations in which specific lipids come together in separate domains (Figure 10–12).
There has been a long debate among cell biologists about whether the lipid molecules in the plasma membrane of living cells similarly segregate into specialized domains, called lipid rafts. Although many lipids and membrane proteins are not distributed uniformly, large-scale lipid phase segregations are rarely seen in living cell membranes. Instead, specific membrane proteins and lipids are seen to concentrate in a more temporary, dynamic fashion facilitated by protein– protein interactions that allow the transient formation of specialized membrane regions (Figure 10–13). Such clusters can be tiny nanoclusters on a scale of a few molecules, or larger assemblies that can be seen with electron microscopy, such as the caveolae involved in endocytosis (discussed in Chapter 13). The tendency of mixtures of lipids to undergo phase partitioning, as seen in artificial bilayers (see Figure 10–12), may help create rafts in living cell membranes—organizing and concentrating membrane proteins either for transport in membrane vesicles
Figure 10–12 Lateral phase separation in artificial lipid bilayers. (A) giant liposomes produced from a 1:1 mixture of phosphatidylcholine and sphingomyelin form uniform bilayers. (B) By contrast, liposomes produced from a 1:1:1 mixture of phosphatidylcholine, sphingomyelin, and cholesterol form bilayers with two separate phases. the liposomes are stained with trace concentrations of a fluorescent dye that preferentially partitions into one of the two phases. the average size of the domains formed in these giant artificial liposomes is much larger than that expected in cell membranes, where “lipid rafts” (see text) may be as small as a few nanometers in diameter. (A, from n. Kahya et al., J. Struct. Biol. 147:77–89, 2004. With permission from elsevier; B, courtesy of petra Schwille.) (discussed in Chapter 13) or for working together in protein assemblies, such as when they convert extracellular signals into intracellular ones (discussed in Chapter 15).