Membrane lipid frustration: Contribution of ceramide and its effects on lateral segregation

Ceramides are both sphingolipid precursor molecules and breakdown products with effects on membranes that are of interest both from biophysical and physiological points of view. When present in a membrane, ceramide induces the formation of highly ordered domains. Ceramide accumulation in biological membranes has in turn been suggested to be involved in committing the cell to death, possibly through effects on membrane fluidity or as a signalling molecule involved in the apoptotic cascade. Though ceramide aggregates at low concentrations in the membrane, this effect can be promoted by other major membrane lipids. Notably some of these are lipids typical of mitochondria, which also is the proposed site of ceramide mediated apoptotic induction. In the interaction of ceramide with its co-lipids the proportion of the headgroup size to the volume occupied by acyl chains appeared as an important factor to consider along with alterations of the hydrogen bonding competency of ceramide itself to other surrounding lipids. The promoted lateral segregation of ceramide by co-lipid molecular shape seems to be driven by different mechanisms. Lipids with proportionally small headgroups interact unfavourably with ceramide which as a result is pushed away, while lipids with large headgroups and small acyl chain volume provides shielding from the aqueous environment.