Fluid-Fluid Phase Separation in Cholesterol-Containing Membranes: Rafts and Non-Rafts

Abstract

Fluid-fluid phase separation is the functionally important mode of in-plane domain formation in lipid-bilayer membranes. The most common, if not sole, well-established case of fluid phase separation is that between liquid-ordered (Lo) and liquid-disordered (Lα) phases in cholesterol-containing membranes. The liquid-ordered phase is characterised by short-range orientational order, but long-range translational disorder. It is well documented for gel-fluid (Lα-Lo) phase coexistence in binary lipid mixtures with cholesterol but, surprisingly, direct evidence for the functionally significant fluid-fluid (Lα-Lo) phase coexistence is rather sparse. Interestingly, evidence for Lα-Lo coexistence is more abundant in ternary mixtures of a high-chain-melting lipid and a low-chain-melting lipid with cholesterol than in binary mixtures. Here, I shall review the current status of the field: it seems that no aspect is without some controversy. Published phase diagrams for the canonical “raft” lipid mixtures, N-palmitoyl sphingomyelin/palmitoyl-oleoyl phosphatidylcholine/cholesterol will be compared, and also new spin-label EPR results on this system will be presented.Marsh, D., 2009. Cholesterol-induced fluid membrane domains: a compendium of lipid-raft ternary phase diagrams, Biochim. Biophys. Acta 1788, 2114-2123.Marsh, D., 2010. Liquid-ordered phases induced by cholesterol: a compendium of binary phase diagrams, Biochim. Biophys. Acta 1798, 688-699.