Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

572 Chapter 10: Membrane Structure
20–25-carbon-long prenyl chains instead of fatty acids; prenyl and fatty acid
chains are similarly hydrophobic and flexible (see Figure 10–20F); in thermophilic
archaea, the longest lipid chains span both leaflets, making the membrane
particularly stable to heat. Thus, lipid bilayers can be built from molecules with
similar features but different molecular designs. The plasma membranes of most
eukaryotic cells are more varied than those of prokaryotes and archaea, not only
in containing large amounts of cholesterol but also in containing a mixture of different
phospholipids.
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
(A)
(B)
10 µm 5 µm
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.)