Modeling lipid raft domains containing a mono-unsaturated phosphatidylethanolamine species

Abstract

Several membrane proteins are preferentially partitioned in lipid microdomains called rafts. The hypothesis of an intimate relationship between proteins and their specific raft environment is nowadays widely accepted. Indeed, the raft–protein cross-talk would influence protein activity and trafficking either by specific lipid–protein interactions or changes in physico-chemical properties of the bilayer. Although lipid rafts used to be simply considered membrane patches enriched in sphingolipids, cholesterol, and saturated phosphocholine derivatives, the optimization of extraction procedures and recent lipidomic analyses challenged this established concept, highlighting a significant presence of phosphatidylethanolamine species. Relying on this evidence, we devised a generic coarse-grained raft-like model containing di-stearoyl phosphatidylcholine, cholesterol and palmitoyl-oleoyl phosphatidylethanolamine species. The model was validated against available experimental data by studying the lipid mixture at different molar ratios through extended molecular dynamics simulations. The agreement of structural and dynamical properties with those of a liquid-ordered crystalline phase suggests that our model can represent a reliable lipid environment especially suited for computational studies aimed at unraveling raft–protein functional interactions.