PERMEABILITY PROPERTIES OF STEROL-CONTAINING LIPOSOMES FROM ANALOGS OF PHOSPHATIDYLCHOLINE LACKING ACYL-GROUPS

The effect of sterols on the rates of nonelectrolyte movement in multilayered liposomal membranes formed from various phosphatidylcholine (PC) analogues was studied. We measured the temperature dependence of the permeation of small, polar solutes through lipid bilayers in the liquid-crystalline state of the following saturated phosphatidylcholines: diesters containing 14, 16, or 18 carbon atoms in each acyl chain; the corresponding diethers, which lack the carbonyl groups; and alkyl analogues, such as 2-octadecyleicosylphosphorylcholine (OEPC), which have no diacylglycerol or glycerol diether moiety. In addition, a diether-PC having one saturated and one unsaturated chain was used, and analogues of OEPC were synthesized in which the choline group is modified. At temperatures above the gel to liquid-crystalline phase transition of these diester, diether, and alkyl analogues of PC, the 3β-hydroxysteroids cholesterol and ergosterol decreased the permeability of glycerol, urea, acetamide, and glucose, whereas epicholesterol and lanosterol exerted little effect on the reflection coefficient for acetamide penetration. Cholesterol reduced solute permeability in liposomes from OEPC analogues having increased separation between the phosphoryl and quaternary ammonium groups of the phosphorylcholine moiety or increased steric bulk in the choline moiety and in the quaternary ammonium group. The activation energy and activation entropy for osmotic swelling of liposomes by glycerol and urea permeation and for fluorescence change of a liposome-associated merocyanine dye upon acetamide permeation were not altered significantly by cholesterol incorporation (48 mol %) into bilayers with the diester or diether phosphatidylcholines we examined. The similarities between the effects of sterols on the initial rates and reflection coefficients of polar nonelectrolyte diffusion in diester-PC bilayers and those from our phospholipids lacking acyl groups (diether-PC and OEPC analogues) indicate that carbonyl oxygens of the fatty acyl groups in the 1 and 2 positions of PC are not essential to obtain interaction with cholesterol. Thus, there is no specific requirement for hydrogen bonding between the hydrogen of the sterol hydroxyl group and a carbonyl oxygen of diester-PC. The studies with OEPC analogues suggest that no rigid structural specificity in the choline moiety of phosphorylcholine must be met for lecithin-cholesterol interaction. © 1979, American Chemical Society. All rights reserved.