Influence of molecular packing and phospholipid type on rates of cholesterol exchange.

The rates of [14C]cholesterol transfer from small unilamellar vesicles containing cholesterol dissolved in bilayers of different phospholipids have been determined to examine the influence of phospholipid-cholesterol interactions on the rate of cholesterol desorption from the lipid-water interface. The phospholipids included unsaturated phosphatidylcholines (PC's) (egg PC, dioleoyl-PC, and soybean PC), saturated PC (dimyristoyl-PC and dipalmitoyl-PC), and sphingomyelins (SM's) (egg SM, bovine brain SM, and N-palmitoyl-SM). At 37 degrees C, for vesicles containing 10 mol% cholesterol, the half-times for exchange are about 1, 13, and 80 h, respectively, for unsaturated PC, saturated PC, and SM. In order to probe how differences in molecular packing in the bilayers cause the rate constants for cholesterol desorption to be in the order unsaturated PC greater than saturated PC greater than SM, nuclear magnetic resonance (NMR) and monolayer methods were used to evaluate the cholesterol physical state and interactions with phospholipid. The NMR relaxation parameters for [4-13C]cholesterol reveal no differences in molecular dynamics in the above bilayers. Surface pressure (pi)-molecular area isotherms for mixed monolayers of cholesterol and the above phospholipids reveal that SM lateral packing density is greater than that of the PC with the same acyl chain saturation and length (e.g., at pi = 5 mN/m, where both monolayers are in the same physical state, dipalmitoyl-PC and palmitoyl-SM occupy 87 and 81 A2/molecule, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)