Cholesterol modulates the effects of membrane perturbers in phospholipid vesicles and biomembranes

Abstract

The order parameter of spin-labeled phosphatidylcholine vesicles has been shown to increase upon incorporation of cholesterol, cannabinol, chlorpromazine and pentobarbital. Cannabinol was as effective on a mole basis as cholesterol in increasing the order parameter of 5-doxyl stearic acid in phosphatidylcholine: 4% phosphatidic acid bilayers at low concentrations. The average increase in order parameter with chlorpromazine and pentobarbital was two to three times less than that of cholesterol. Relative to cholesterol these compounds were less effective at ordering 1-acyl-2[8(4,4-dimethyloxazolidine- N-oxyl)] palmitoyl phosphatidylcholine. The ordering effect with any given membrane perturber became smaller when increasing amounts of cholesterol were incorporated in the phospholipid bilayers until a disordering effect was finally observed. The cholesterol composition at which this cross-over from ordering to disordering occurred varied with the perturber, being 26 mole % for chlorpromazine, 23 mole % for cannabinol and 14 mole % for pentobarbital. The ability of cholesterol itself to increase the order parameter of the bilayer was decreased in the presence of these perturbers. These compounds may exert their ordering effect on the interfacial region of phospholipid bilayers in an analogous manner to cholesterol. However, at higher cholesterol contents their additional ordering effect is more than counterbalanced by a weakening of the cholesterol-acyl interaction and a net disordering effect results. In biological membranes a similar role for cholesterol in modulating the effect of perturbers was observed. Cannabinol decreased the order of erythrocyte membranes but increased that of mitochondrial membranes, while octanol disordered both of these biological membranes.