The solubility of cholesterol and its exchange between membranes

It has been proposed that exchange between membrane cholesterol pools occurs by desorption of molecules into the aqueous environment rather than by formation of a transitory collision complex between the membranes. The rate of exchange is likely to be determined by the rate of dissociation of cholesterol from the membrane bilayer and by the concentration of cholesterol monomers or aggregates of cholesterol molecules in solution. The aim of this study was to measure the effects of agents known to increase cholesterol exchange rates on cholesterol solubility, critical micellar concentration and on the activation energy of exchange. A comparison was also made with regard to these parameters, of the exchange of cholesterol to that of 4-cholesten-3-one, another steroid which exchanges more rapidly than cholesterol. Acetone and dimethylsulphoxide increased cholesterol exchange between liposomes and erythrocytes, but only modestly increased the apparent solubility of cholesterol in saline and had no effect on the activation energy of the exchange process. However, acetone and dimethylsulphoxide increased the critical micellar concentration of the cholesterol 3-fold, although tetraethylammonium iodide, which had a smaller effect on exchange, did not. 4-Cholesten-3-one had a lower solubility and critical micellar concentration than that of cholesterol, but had the same activation energy for exchange. It is concluded that the apparent solubility of steroid aggregates are unlikely to determine the rate of exchange, but that agents which substantially increase exchange also increase the critical micellar concentration. The low critical micellar concentration of cholestenone suggests that the actual monomer concentration in an exchange system is low and that the rate of dissociation of the molecules from the liposomes must determine the exchange rate. This is not reflected in the activation energy measurements since these are a composite of all the elements of the exchange process.