Abstract
Cholesterol's role in ordering lipid membrane domains is well known. Even subtle changes in the structure of this sterol greatly affect the biophysical dynamics of membranes, usually because of perturbations in the interactions between the sterol and other membrane lipids that chemical modifications cause.Cholesterol oxidation products (oxysterols), which result from enzymatic and non-enzymatic mechanisms, are cytotoxic and found in atherosclerotic plaques. Previous studies have shown that the membrane properties of oxysterols vary, depending on the specific site of the oxygen-containing moiety. In this study, we examined the interactions of two oxysterols, one formed through non-specific oxidation (7-ketocholesterol), and one produced enzymatically (25-hydroxycholesterol) with two common membrane lipids, 1-palmitoyl-2-oleoyl-sn-phosphocholine (POPC) and brain-derived sphingomyelin.Analysis of force-area isotherms obtained by compression of pure sterol monolayers and of binary monomolecular films at the air-water interface, comprised of varying mole fractions of POPC or sphingomyelin and either oxysterol, reveals significant differences in surface behavior with respect to each other and to native cholesterol. Both oxysterols condensed POPC and sphingomyelin films to a lesser degree than cholesterol, and an expansion of sphingomyelin films was observed with low mole fraction 7-ketocholesterol. Additionally, surface compression moduli data obtained from the force-area isotherms reveal a decreased ability of both oxysterols to mitigate the phase transition of sphingomyelin compared to cholesterol. The changes of membrane behavior in the presence of oxysterols reported here suggest a relation of their toxicity to the propensity of lipids membranes to form liquid-ordered domains (rafts).
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