COMPARISON OF THE EFFECTS OF CHOLESTEROL AND OXYSTEROLS ON PHOSPHOLIPID-BILAYER MICROHETEROGENEITY - A STUDY OF FLUORESCENCE LIFETIME DISTRIBUTIONS

The homogenizing effect of cholesterol and its oxidative derivatives, 7-ketocholesterol, cholesterol 5 alpha,6 alpha-epoxide and 25-hydroxyc holestero1, in liquid-crystalline 1,2-dioleoyl-sn-glycero-3-phosphocho line (DOPC) bilayer vesicles was studied using the fluorescence lifeti mes of panoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (DPH-PC). Th e phase and modulation data were fitted either to discrete exponential models or to models characterized by continuous distributional lifeti mes. Among all the models tested, it was found that the best one to ac count for the experimental data was the unimodal Lorentzian distributi on. Thus, the DPH-PC lifetime was adequately described by a distributi onal center and a full width at half-maximum, for DOPC vesicles these values being 6.23 and 0.48 ns, respectively. Increasing the concentrat ion of cholesterol, 7-ketocholesterol, or cholesterol 5 alpha,6 alpha- epoxide from 0 to 30 mol% resulted in an increase of the lifetime cent er (e.g., 7.16 ns at 30 mol% cholesterol) and a decrease of the distri butional width (e.g., 0.05 ns at 30 mol% cholesterol). On the other ha nd, up to 30 mol% of 25-hydroxycholesterol incorporated into the bilay er vesicles showed little influence on both lifetime parameters. Our r esults support the use of lifetime distributional width to evaluate me mbrane heterogeneity and suggest that oxysterols, depending on their m olecular structural particulars, may exert cholesterol-like homogenizi ng effect in membranes. (C) 1994 Academic Press, Inc.