Page 103 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

P1: GST/MBQ P2: GQT Final Pages
Encyclopedia of Physical Science and Technology EN009G-417 July 10, 2001 15:10

364 Membrane Structure

As far as lipid headgroups are compared, addition of higher melting components are dispersed as minor compo-
cholesterol increases the chain order in the sequence 18:0– nents of total lipid in a host matrix consisting of, for exam-
18:1 PS < 18:0–18:1 PC < 18:0–18:1 PE for the monoun- ple, 1-stearoyl-2-oleoyl-phosphatidylcholine and choles-
saturated lipid mixture and in the sequence 18:0–22:6 terol, neither short-chain nor long-chain cerebrosides or
PS < 18:0–22:6 PE 18:0–22:6 PC for polyunsaturated sphingomyelins show phase separation in the physiolog-
mixtures. The cholesterol-induced variation of order pa- ical temperature range despite their high phase transition
rameters as a function of the chemical nature of the lipid temperatures.
species suggests a cholesterol-induced formation of lipid Mixtures of cholesterol and sphingolipids have recently
microdomains with a headgroup- and fatty-acyl-chain- attracted attention since spingolipid–cholesterol domain
dependent lipid composition. In particular, under phys- formation has been observed in mammalian cell mem-
◦
iological conditions, the formation of PC-enriched mi- branes upon cooling to 4 C and extraction with Triton
crodomains has been proposed in which the saturated X-100. This phenomenon has also been termed “lipid raft”
sn-1 chain is preferentially oriented toward the choles- formation. Lipid rafts exhibit a high lateral packing den-
terol molecule. The lifetime of a lipid molecule in a given sity and are suggested to entail a sorting of GPI-anchored
cluster, however, is less than 10 −4 s, and the cluster radius proteins. The bulky intrinsic proteins remain in the fluid
is probably smaller than 25 nm. phase. At room temperature, lipid rafts are no longer de-
In a natural membrane the effect of cholesterol is very tectable. Nevertheless, they are assumed to prevail as mi-
similar as in model membranes. This was shown, for ex- crodomains at growth temperature and to be relevant for
ample, for Acholeplasma laidlawii membranes by the in- membrane trafficking and protein sorting in mammalian
corporation of perdeuterated and selectively deuterated cells.
fatty acids. Although domain formation is now a common theme
among biologists, an unambiguous physical–chemical
characterization of domains under physiological condi-
V. PHASE BEHAVIOR OF LIPIDS AND tions is still missing. On physical grounds, domain for-
MEMBRANE DOMAIN FORMATION mation is most likely to occur in mixtures of lipids with
widely different gel-to-liquid crystal phase transition tem-
A large number of phase diagrams for binary mixtures peratures. Phase separation will occur if the measuring
combining cholesterol with different saturated and unsatu- temperature is below the phase transition temperature of
rated phosphatidylcholines have been established. Choles- one of the components of the mixture and if this compo-
terol at different bilayer concentrations can promote or nent constitutes a major lipid fraction. Lipids exhibiting
suppress lateral segregation of phospholipids of differing highphasetransitiontemperaturesgenerallyhavelongsat-
acyl chain length. urated acyl chains and small headgroups, or headgroups
Addition of 50 mol% cholesterol to selectively deuter- that may interact via hydrogen bonding. Typical exam-
ated DPPC bilayers leads to an elimination of the gel-to- ples are sphingolipids, glycosphingolipids, or long-chain
liquid crystal phase transition at 41 C. In contrast, choles- phosphatidylethanolamines.
◦
terol is also found to enhance the tendency of the PC As a further mechanism, electrostatic interactions of
components to exhibit lateral segregation. These seem- anionic lipids with cationic compounds may also induce
ingly contradictory effects of cholesterol can be readily domain formation. Due to the biochemical complexity
explained in light of the cholesterol–phospholipid phase of biological membranes, the molecular mechanisms re-
diagrams. sponsible for phase separation are not easily distinguished
The effect of cholesterol on the thermotropic phase experimentally.
behavior of aqueous dispersions of different lipids The difficulty in understanding the diverging results
has been extensively investigated by means of differ- arises, on the one hand, from the use of techniques differ-
ential scanning calorimetry. The results show an in- ing in spatial (nanometers to micrometers) and temporal
verse correlation between the strength of intermolecu- (nanoseconds to tens of seconds) resolution and, on the
lar phospholipid–phospholipid interactions, as manifested other hand, from the application of different experimental
by the gel-to-liquid crystalline phase transition temper- conditions. For technical reasons, domain formation was
atures of the pure phospholipids, and the miscibility generally investigated at unsphyiological temperatures us-
of cholesterol with the respective bilayer (particularly ing lipids with bulky reporter groups. Both factors may af-
gel-state bilayers). The miscibility of cholesterol with fect the phase behavior of lipids. Further experiments are
lipids carrying identical fatty acyl chains decreases in therefore required to test whether oganizational processes
the order: PC ∼ PG ∼ SM > PS > PE > diglucosyl- and are induced by lipid domain formation under physiologi-
monoglucosyl-diacylglycerol > GalCer. However, if the cal conditions.