Cholesterol tilting drives phase separation in lipid bilayer membranes

Abstract

We present a theory that predicts that cholesterol molecules phase separate from multicomponent lipid bilayer membranes, but not from monolayers of the same composition. In our model, the tilting of cholesterol molecules in monolayers is not energetically favorable because their exocyclic chains are very short. However, in bilayers, two correlated cholesterol molecules in the opposing leaflets of bilayers can form “dimers”, whose chains are effectively twice as long and can tilt cooperatively. Our theory predicts that the cooperative tilting of these dimers drives the phase separations of cholesterol in bilayers.