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-hydroxycholesterol, in liquid-crystalline 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC) bilayer vesicles was studied using the fluorescence lifetimes of 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p hosphocholine (DPH-PC). The phase and modulation data were fitted either to discrete exponential models or to models characterized by continuous distributional lifetimes. Among all the models tested, it was found that the best one to account for the experimental data was the unimodal Lorentzian distribution. Thus, the DPH-PC lifetime was adequately described by a distributional center and a full width at half-maximum, for DOPC vesicles these values being 6.23 and 0.48 ns, respectively. Increasing the concentration of cholesterol, 7-ketocholesterol, or cholesterol 5 alpha, 6 alpha-epoxide from 0 to 30 mol% resulted in an increase of the lifetime center (e.g., 7.16 ns at 30 mol% cholesterol) and a decrease of the distributional width (e.g., 0.05 ns at 30 mol% cholesterol). On the other hand, up to 30 mol% of 25-hydroxycholesterol incorporated into the bilayer vesicles showed little influence on both lifetime parameters. Our results support the use of lifetime distributional width to evaluate membrane heterogeneity and suggest that oxysterols, depending on their molecular structural particulars, may exert cholesterol-like homogenizing effect in membranes.
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Department of Biochemistry, Faculty of Medicine, National University of Singapore.
Das
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D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D004161:Diphenylhexatriene / Q000737:chemistry; D006888:Hydroxycholesterols / Q000737:chemistry*; D007653:Ketocholesterols / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; C002415:cholesterol alpha-oxide; D004161:Diphenylhexatriene; C007997:25-hydroxycholesterol; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; C003001:7-ketocholesterol