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

Lipids in all biological membranes are distributed heterogeneously across the bilayer. A particularly striking example of this asymmetry is the yeast plasma membrane, which exhibits a high concentration of very long-chain tail-asymmetric sphingolipids in its outer leaflet. Experimental observations indicate the existence of highly ordered gel-like plasma membrane domains that are enriched in sphingolipids but depleted of 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 tail-asymmetric lipids. In agreement with experimental results, we observed the formation of a gel phase, with a high-order parameter of the acyl chains and hexagonal arrangement of lipid tails, at higher concentrations of these long-chain lipids. By systematically varying the lipid number asymmetry between the two leaflets, we demonstrate that the observed gel phase in asymmetric membranes is a robust feature and not an artifact of membrane construction. 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 timescale.