Evidence for Phase Separation in Model Membrane Systems

Liquid-Ordered and Liquid-Disordered Phases

Various model membrane systems have been used by physicists and chemists to study phase separation in lipid mixtures. They are either monolayers or bilayers. Monolayers are either assembled at an air-water interface with the packing density of the lipids being adjusted by applying lateral pressure, or on a supporting lipid monolayer that is fixed to a solid support. Bilayers are used in the supported version as described above, or in the form of vesicles. The most commonly used vesicles are large or giant unilamellar vesicles (LUV or GUV, respectively) composed of only a single bilayer, but also multilamellar vesicles (MLV) are used. The basic principles were first established in simple binary lipid mixtures, but recently

ternary mixtures which more closely mimic the composition of the cell plasma membrane have been used. The mixtures usually contain one lipid with a high melting temperature (Tm), one with a low Tm, and cholesterol. GUVs are probably the system closest to a cell membrane, because artifacts from a support are excluded. Still, cell membranes are asymmetric with different lipid compositions of the outer versus the inner leaflet, while the GUVs used so far were all symmetric.

Since maintaining an asymmetric lipid distribution is energy-consuming, perhaps by reconstituting lipid translocators into liposomes this drawback can be overcome in the future. Although model membrane systems produce very simplified pictures of cell membranes, there are many examples of a close correlation with experimental data obtained in living cells [14]. Ipsen et al. were the first to describe the formation of a liquid-ordered phase by cholesterol and saturated phospholipids [15,16]. This phase can coexist with other lipid phases, and its characteristics are described as follows: the translational order of lipid molecules within the liquid-ordered phase is similar to that in a fluid bilayer state, whereas the configurational order of the hydrocarbon chains compares more to that in a gel state. The formation of the liquid-ordered phase was attributed to the unique chemical nature of cholesterol (for a review, see [17]), but later it was shown that all natural sterols promote domain formation and that also

small amounts of ceramide (3%) can stabilize domains formed in vesicles [18]. Leventis and Silvius showed that the interaction of cholesterol with different lipid species is dependent on the nature of their hydrocarbon chains and, to a lesser extent, also on their headgroup. The interaction preference decreases with SM > PS > PC > PE and with increasing unsaturation of the acyl chains [19]. Whereas the kink in unsaturated hydrocarbon chains is likely to hinder tight packing with the flat sterol ring of cholesterol, the reason for the preferential interaction of cholesterol with SM is still a debated issue.

Source::

Fielding, J.Christtoper, lipid raft and caveolae . Jhown willey and Son Publishe