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Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: DOI: 10.1017/S1462399402005410; 20 December 2002
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Cholesterol favours phase separation of membrane lipids: the origin of raft formation?

Jacques Fantini, Nicolas Garmy, Radhia Mahfoud and Nouara Yahi

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Figure 2. Cholesterol favours phase separation of membrane lipids: the origin of raft formation? (a) In bilayers of the glycerophospholipid (GPL) phosphatidylcholine below the Tm (melting temperature), the molecules can be packed such that the acyl chains are tilted with respect to the normal bilayer to form a crystalline, solid gel-like phase (Lb), but at 37°C (above Tm) the bilayer converts to a liquid-crystalline, fluid phase (Lc; also sometimes referred to as La). The addition of cholesterol to pure GPLs abolishes the normal thermal transition between Lb and Lc phases, giving membrane properties intermediate between the two phases. This well-known effect of cholesterol initially suggested that the slight differences in the Tm of various GPLs were ‘corrected’ by cholesterol, resulting in a homogeneous lipid phase at the physiological temperature. (b) In contrast to pure GPLs, pure sphingolipids form a gel phase (Lb) at 37°C, with tight packing of the saturated chains. Cholesterol interacts preferentially (although not exclusively) with sphingolipids and favours the phase separation between sphingolipids and GPLs. In the plasma membrane, GPLs form a relatively cholesterol-poor Lc phase, whereas sphingolipids form a liquid-ordered (Lo) phase highly enriched in cholesterol. Rafts probably exist in a Lo phase or a state with similar properties (fig002jfm).

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