Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: DOI: 10.1017/S1462399402005422; 20 December 2002
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Lipid organisation in raft microdomains: a simplified model based on the theoretical shape of membrane lipids

Jacques Fantini, Nicolas Garmy, Radhia Mahfoud and Nouara Yahi

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Figure 3. Lipid organisation in raft microdomains: a simplified model based on the theoretical shape of membrane lipids. The ability of membrane lipids to form the basic bilayer structure is the result of several properties, the most important of which is their amphipathic character. Amphipathic molecules have a polar, hydrophilic head group region and a non-polar, hydrophobic part. In aqueous solvents, amphipathic molecules naturally orientate themselves to ensure that the polar groups associate with water molecules, whereas the hydrophobic chains interact with each other so that a maximal number of water molecules are excluded from the hydrophobic phase. If the lipid is roughly cylindrical in dimension, biplanar leaflets will be the most thermodynamically stable configuration. (a) Glycerophospholipids (GPLs), which form the Lc phase of the plasma membrane (see Fig. 2), are indeed roughly cylindrical; however, cholesterol and sphingolipids [especially glycosphingolipids (GSLs)] have a pyramidal or cone-like shape. In sphingolipids the polar head group occupies a larger area than does the hydrophobic region (Ref. 4), whereas the converse is true for cholesterol. (b) Sphingolipids are almost exclusively found in the external (outer) leaflet of the plasma membrane, where – given the remarkable fit between the global shape of cholesterol and sphingolipids – any void between associated sphingolipids is thought to be filled by cholesterol functioning as a molecular spacer. The enrichment of cholesterol in Lo phase domains (see Fig. 2) is consistent with this model. A close interaction between cholesterol and sphingomyelin has been demonstrated in various reconstituted membrane systems. The tail-to-tail organisation of cholesterol in raft areas could rigidify the cytoplasmic (inner) leaflet of the plasma membrane, which is virtually devoid of sphingolipids but contains selected GPLs (e.g. phosphatidylinositol and phosphatidylethanolamine with saturated acyl chains) with physicochemical properties close to those of sphingomyelin. SM, sphingomyelin (fig003jfm).