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Poking and Sealing Holes : Interactions of Antimicrobial Peptides and Poloxamers with Lipid Membranes

The phase diagrams of some cholesterol-lipid mixtures exhibit two immiscibility regions along with a sharp cusp, pointing to a particular stoichiometry for possible lipid/cholesterol complex formation. It has been hypothesized that reactive cholesterol monomers are present in mixtures with cholesterol content greater than that at the cusp. To test this hypothesis, we have examined how the presence of alcohol alters the lipid/cholesterol phase diagram. Lipid/cholesterol/alcohol systems in which various mole fractions of cholesterol are replaced by alcohol reproduce the identical phase diagram as the lipid/cholesterol system, with the cusp position unaltered. Cholesterol uptake by beta-cyclodextrin is large in the ternary system as long as the combined mole fraction of cholesterol and alcohol exceed that at the cusp. X-ray diffraction on these mixtures shows the presence of a broad Bragg peak, indicative of the existence of crystalline order, with coherence length of several molecular dimensions, in mixed lipid/cholesterol systems.