Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes

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Abstract
Pressure versus distance relationships have been obtained for egg phosphatidylcholine bilayers containing a range of cholesterol concentrations. Water was removed from between ajacent bilayers by the application of osmotic pressuresin the range of 0.4.sbd.2600 atm (4 .times. 105.sbd.2.6 .times. 109 dyn/cm2), and the distance between adjacent bilayers was obtained by Fourier analysis of X-ray diffraction data. For applied pressures up to about 50 atm and bilayer surface separations of 15.sbd.5 .ANG., the incorporation of up to equimolar cholesterol has little influence on plots of pressure versus bilayer separation. However, for the higher applied pressures, cholesterol reduces the interbilayer separation distance by an amount that depends on the cholesterol concentration in the bilayer. For example, the incorporation of equimolar cholesterol reduces the distance between bilayers by as much as 6 .ANG. at an applied pressure of 2600 atm. At this applied pressure, electron density profiles show that the high-density head-group peaks from apposing bilayers have merged. This indicates that equimolar concentrations of cholesterol spread the lipid molecules apart in the plane of the bilayer enough to allow the phosphatidylcholine head groups from apposing bilayers to interpenetrate as the bilayers are squeezed together. All of these X-ray and pressure.sbd.distance data indicate that, by reducing the volume fraction of phospholipid head groups, cholesterol markedly reduces the steric repulsion between apposing bilayers but has a much smaller effect on the sum of the longer ranged repulsive hydration and fluctuation pressures. Increasing concentrations of cholesterol monotonically increase the dipole potential of egg phosphatidylcholine monolayers, from 415 mV with no cholesterol to 493 mV with equimolar cholesterol. These dipole measurements predict that cholesterol should increase slightly the magnitude of the hydration pressure, in qualitative agreement with the X-ray results. These observations are pertinent to cholesterol''s role in vesicle adhesion and fusion and also imply that cholesterol can alter the membrane binding and permeability of ions and certain drugs and metabolites.