Lateral phase separation in mixtures of lipids and cholesterol systems

– In an effort to understand “rafts” in biological membranes, we propose phenomenological models for saturated and unsaturated lipid mixtures, and lipid-cholesterol mixtures. We consider simple couplings between the local composition and internal membrane structure, and their influence on transitions between liquid and “gel” membrane phases. Assuming that the gel transition temperature of the saturated lipid is shifted by the presence of the unsaturated lipid, and that cholesterol acts as an external field on the chain melting transition, a variety of phase diagrams are obtained. The phase diagrams for binary mixtures of saturated/unsaturated lipids and lipid/cholesterol are in semi-quantitative agreement with the experiments. Our results also apply to regions in the ternary phase diagram of lipid/lipid/cholesterol systems. Introduction. – Biological membranes typically contain various components such as lipid mixtures, sterols, and proteins that are indispensable to cell functions [1]. Rather than being uniformly distributed in the membrane, there is growing evidence that some intra-membrane components are incorporated in domains arising from lateral lipid segregation in membranes. This phenomena has attracted great interest in the context of “rafts” [2], i.e., liquid domains rich in cholesterol, saturated lipids (typically sphingomyelin lipids), and in some cases particular proteins [3]. Moreover, cholesterol-rich domains have been directly observed in model membranes composed of lipid mixtures and cholesterol, using advanced fluorescence microscopy [4, 5, 6, 7, 8, 9, 10]. Prior to the notion of “rafts” in biological membranes, the role of cholesterol was investigated in binary lipid-cholesterol membranes [11,12,13], where phase separation was observed using NMR and calorimetry [14, 15]. Lipid membranes undergo a freezing or “gel-like” transition, in which the hydrocarbon tails order. Addition of cholesterol has several effects. It () E-mail: [email protected]