The rate of cholesterol ‘flip-flop’ in lipid bilayers and its relation to membrane sterol pools

Abstract

The movement of lipid molecules from one side of a lipid bllayer to the other (the so-called ‘flip-flop’) was first studied in films of stearate [I]. At 25°C stearate molecules transferred with a halftime of 25 min in the absence of Ca2 + and 50 min in its presence. Of more relevance to cellular membranes is the ‘flipflop’ of the major structural lipids, phospholipids and unesterified sterols. Phospholipid transfer has been investigated by a spin-labelling technique in liposomes of egg lecithin [2] . The half-time at 30°C was 6.5 hr and the process is at least eight orders of magnitude slower than translational migration within the plane of the bilayer [3]. We have now utilized the ability of iodide ions added to one side of a lipid bilayer to quench the fluorescence of the sterol sterophenol (l-methyl19nor-cholesta-1,3,5( 1 O)trien-3-01; fig. 1) on that side of the bilayer, to measure sterol ‘flipflop’ in liposo mes. The process is much faster than that of phospho lipids, with a half-time at 3O’C of 72 min. This finding is of relevance to studies of cholesterol exchange between plasma lipoproteins and cell membranes and to the finding in such studies [4,5] of more than one pool of membrane sterol.