Organization of glycosphingolipids in bilayers and plasma membranes of mammalian cells.

The evidence presented in this review strongly suggests that, when present as a minor component in liquid crystalline phospholipid bilayers, neutral glycosphingolipids are segregated into compositional domains of small size dispersed in the matrix phospholipid. In many instances the glycosphingolipid in the dispersed domains is in the gel state. Because these domains are in the gel state, the individual molecules escape only very slowly from the surface of the bilayer, much more slowly than do the phospholipid components. There is as yet no direct evidence that this slow escape rate is a property of neutral glycolipids in biological membrane bilayers. If it is, however, then these molecules are well suited for their putative role as cell surface markers, a role that involves them in many important biological functions. There is evidence to suggest that molecules of this type are also present in a dispersed microdomain structure on the external surface of at least some mammalian cell plasma membranes. These small domains of glycolipids with their sugar residues projecting outward from the cell surface are much like a large membrane glycoprotein when viewed from the ambient medium near the cell surface. Thus, whether the sugar residues be of glycoprotein or glycolipid origin, they are localized in groups or patches on the external surface of the cell. One important consequence of this patch structure may be in the obvious effect on the free energy of binding a ligand to a patch. Whether the ligand is mono- or polyvalent, the roughly 2 M concentration of sugar in the surface patch will cause the apparent ligand binding free energy to be substantially larger than it would be for a single isolated sugar residue on the surface. In contrast to the neutral glycosphingolipids (and sulfatides, perhaps) the available information suggests that gangliosides are not localized in small domains in model systems and most probably not in biological membranes. Capping of this type of glycosphingolipid does appear to occur under certain circumstances. However, it is almost certain that capping is not an intrinsic property of ganglioside phospholipid-bilayer systems. Although at 37 degrees C gangliosides rapidly transfer from micelles to phospholipid vesicles and to cell membranes, nothing is known about the rates at which this class of molecules leave a phospholipid bilayer. Their known biological functions on the cell surface appear to require that they leave very slowly, if at all, as do the neutral glycosphingolipids. The glycosphingolipids are, by virtue of their polysaccharide moeity, a unique class of lipids and cell surface components.(ABSTRACT TRUNCATED AT 400 WORDS)