Biology Reference
In-Depth Information
solvent.
1
Within this model, membrane lipids have been thought to
distribute mostly homogeneously and play minor functions in mem-
brane phenomena. A current concept of lipid rafts refined this classical
model, proposing instead that the membrane lipids actively participate
in the regulation of membrane functions by forming laterally organized
microdomains that selectively incorporate or exclude membrane pro-
teins.
2
This concept has had a great impact on studies of membrane traf-
ficking and signal transduction. It also provided a new view to allow
understanding of how viruses regulate their viral proteins by specifying
interactions with membrane lipids to promote their replication cycles.
Membrane Lipids Form Functional Microdomains
Biological cell membranes are composed primarily of phospholipids
(sphingomyelin and glycerophospholipids), glycolipids (mostly gly-
cosphingolipids), and cholesterol (Fig. 1A). Phospholipids and glycol-
ipids have two acyl-chain tails. Membrane fluidity is affected by the
degree of saturation and by the length of these acyl-chains. Since both
acyl-chains of sphingolipids (sphingomyelin and glycosphingolipids) are
usually saturated and longer than those of glycerophospholipids (phos-
phatidylethanolamine, phosphatidylserine, and phosphatidylcholine),
these lipids tend to pack more tightly against one another than glyc-
erophospholipids. On the other hand, one of the acyl-chains of glyc-
erophospholipids is usually kinked by
cis
-double bonds (unsaturated),
causing glycerophospholipids to have weak interactions with one
another. As a result, membrane lipids of bilayers composed predomi-
nantly of glycerophospholipids are disordered and highly fluid; that is,
they reside in a liquid-disordered, or liquid-crystalline (lc), phase
(Fig. 1B). Cholesterol molecules take their positions between phos-
pholipids and glycolipids, strengthening the order of these lipids. With
cholesterol, sphingolipids become highly ordered without losing their
rotational and lateral mobility, and reside in a liquid-ordered (lo) phase
3
(Fig. 1B). Since lipid molecules in lo phase are insoluble in solutions of
nonionic detergents at low temperature (such as 0.25-1.0% Triton X100
at 4
C), it is possible to isolate them from low-density fractions after
floatation in sucrose gradients.
4
Using this method, it has been shown
that biologcal membranes contain cholesterol and sphingolipid-rich
°
