The dynamic softening and intrinsic stiffening effect of cholesterol on membranes

Small patches of the plasma membrane of the cell must be reshaped from a nearly flat geometry into a sphere (vesicle) as part of the normal transport of proteins and lipids inside as well as out of the cell. The key parameter characterizing how the membrane resists this deformation is the bending modulus, the force constant for membrane curvature deformations.

The plasma membrane of cells is made up of hundreds of different types of lipids. Each of these lipids has a varied effect on membrane mechanical properties, including the bending modulus. Cholesterol is both the most abundant single lipid species as well as the most unusual, having a rigid ring structure that, consistent with intuition, often does strongly perturb the mechanics of simple model membranes.

Molecular simulation evidence will be presented demonstrating that the effect of cholesterol varies with the surrounding composition of the lipid matrix. The key parameter appears to be its preference for concave membrane leaflet curvature. Depending on how strongly cholesterol couples to local curvature, it may have a dramatic softening effect at long timescales, and/or a strong stiffening effect at short timescales. This complex behavior may be at the heart of discrepancies between techniques that measure the stiffness response at short timescales or at equilibrium.