Contrary Effects of Cholesterol on Single-Component and Synaptic Vesicle Mimicking Lipid Bilayers

Cholesterol is a major determinant of biological lipid membrane properties. Its physiological levels are affected by widely used prescription drugs. The effect of changing the cholesterol content has been extensively studied in model lipid bilayers, but it still remains a matter of debate. Here we compare the effect of cholesterol on synaptic vesicle-mimicking (consisting of POPE, POPC, POPS) and single-component bilayers (containing POPC). We quantify the effects of cholesterol on the mechanical properties of the membrane (e.g., lipid packing, polarity, and the force needed for an AFM tip to break through the bilayer), and their relationship to membrane fusion. Cholesterol increases lipid chain packing both in PC/PE/PS and in POPC. However, in PC/PE/PS, contrary to POPC, cholesterol decreases the breakthrough force and accelerates spontaneous vesicle fusion. So, cholesterol may drive the properties of specific biological membranes in a direction that is opposite to that observed for simpler bilayers.