Effect of very long-chain lipids on the organization of biological membranes: A simulation perspective

Lipids in all biological membranes are distributed heterogeneously across the bilayer. A particularly striking example for this asymmetry is the yeast plasma membrane (PM), which exhibits a high concentration of very long-chain sphingolipids (SL) in its outer leaflet. Experimental observations indicate the existence of highly ordered gel-like PM domains that are enriched in SL but depleted in the major yeast sterol ergosterol. For a better mechanistic understanding of these unusual domains we have performed coarse-grained molecular dynamics simulations with membranes containing varying concentrations of very long-chain lipids. In agreement with experimental results we observed formation of a gel phase, with high order parameter of the acyl chains and hexagonal arrangement of lipid tails, at higher concentrations of very long-chain lipids. Our simulations also show that ergosterol is excluded from these gel regions and that, even when embedded into a liquid disordered phase, gels remain stable on the simulation time scale.