PHYSICAL EFFECTS OF BIOLOGICALLY FORMED CHOLESTEROL OXIDATION-PRODUCTS ON LIPID-MEMBRANES INVESTIGATED WITH FLUORESCENCE DEPOLARIZATION SPECTROSCOPY AND ELECTRON-SPIN-RESONANCE

Planar oriented membranes of 1-palmitoyl, 2-oleoyl-phosphatidylcholine (POPC) containing cholesterol, 19-hydroxycholesterol, 22S-hydroxychol esterol, or 25-hydroxycholesterol in concentrations up to 5 mol % were investigated with angle-resolved fluorescence depolarization and elec tron spin resonance measurements. Analyses of the data with the Browni an diffusion model show that the oxysterols have structural effects si milar to those of cholesterol: an increase in molecular order and no c hange in the rotational diffusion coefficients of the probe molecules. Time-resolved fluorescence anisotropy measurements on diphenylhexatri ene (DPH) in small unilamellar vesicles of POPC and DOPC were performe d using oxysterols commonly found in oxidized low density lipoproteins (LDL) in comparison to membranes containing lipoproteins (LDL) in com parison to membranes containing cholesterol or no sterols. Analyses us ing the Brownian rotational diffusion model show that most LDL-oxyster ols affect the vesicle physical structure in a manner similar to chole sterol, viz. an increase in molecular order and a decrease in the dyna mics. Cholesterol-alpha-epoxode has a much smaller ordering effect tha n cholesterol in POPC-vesicles. A similar effect was found for 7 beta- hydroxycholesterol in DOPC-vesicles. The tendency of the oxysterols to influence the molecular order as compared to pure cholesterol may con tribute to cell membrane permeability changes affecting crucial cell f unctions and events leading to vascular cell injury. Increased LDL oxy sterol levels may account for some of the structural changes noted for oxidatively modified LDL as well as its toxicity to vascular cells.