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Effect of Membrane Characteristics on Phase Separation and Domain Formation in Cholesterol-Lipid Mixtures

Department of Chemical Engineering, Drexel University, Philadelphia, Pennsylvania 19104

Correspondence: Address reprint requests to Nily Dan, Dept. of Chemical Engineering, CAT Bldg. 27A-479, Drexel University, Philadelphia PA 19104. Tel.: 215-895-6624; E-mail: dan{at}coe.drexel.edu.

We examine, using an analytical mean-field model, the distribution of cholesterol in a lipid bilayer. The model accounts for the perturbation of lipid packing induced by the embedded cholesterol, in a manner similar to that of transmembrane proteins. We find that the membrane-induced interactions between embedded cholesterol molecules vary as a function of the cholesterol content. Thus, the effective lipid-cholesterol interaction is concentration-dependent. Moreover, it transitions from repulsive to attractive to repulsive as the cholesterol content increases. As the concentration of cholesterol in the bilayer exceeds a critical value, phase separation occurs. The coexistence between cholesterol-rich and cholesterol-poor domains is universal for any bilayer parameters, although the composition of the cholesterol-rich phase varies as a function of the lipid properties. Although we do not assume specific cholesterol-lipid interactions or the formation of a lipid-cholesterol cluster, we find that the composition of the cholesterol-rich domains is constant, independent of the cholesterol content in the bilayer.

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