Effects of ceramide and other simple sphingolipids on membrane lateral structure

The available data concerning the ability of ceramide and other simple sphingolipids to segregate laterally into rigid, gel-like domains in a fluid bilayer has been reviewed. Ceramides give rise to rigid ceramide-enriched domains when their N-acyl chain is longer than C12. The high melting temperature of hydrated ceramides, revealing a tight intermolecular interaction, is probably responsible for their lateral segregation. Ceramides compete with cholesterol for the formation of domains with lipids such as sphingomyelin or saturated phosphatidylcholines; under these conditions displacement of cholesterol by ceramide involves a transition from a liquid-ordered to a gel-like phase in the domains involved. When ceramide is generated in situ by a sphingomyelinase, instead of being premixed with the other lipids, gel-like domain formation occurs as well, although the topology of the domains may not be the same, the enzyme causing clustering of domains that is not detected with premixed ceramide. Ceramide-1-phosphate is not likely to form domains in fluid bilayers, and the same is true of sphingosine and of sphingosine-1-phosphate. However, sphingosine does rigidify pre-existing gel domains in mixed bilayers.