Fluorocholesterols, In Contrast To Hydroxycholesterols, Exhibit Interfacial Properties Similar To Cholesterol

Fluorocholesterols, In Contrast To Hydroxycholesterols, Exhibit Interfacial Properties Similar To Cholesterol

Kauffman J M; Westerman P W; Carey M C

Journal of Lipid Research

2000

2000-06

We used an automated Langmuir-Pockels surface balance to characterize the air-water interfacial properties of cholesterol (CH) and its derivatives with hydrophilic OH and F substitutions at isologous sites on the sterol body or side chain. We studied 6-fluorocholesterol, 25-fluorocholesterol, 25,26,26,26,27,27,27-heptafluorocholesterol, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, alone and in mixtures with 1-palmitoyl-2-oleoyl-sn-3-glycero-phosphocholine (POPC). Pressure-area isotherms of the fluorocholesterols were essentially indistinguishable from CH and all condensed POPC monomolecular layers (monolayers) to variable degrees. Both nucleus-substituted hydroxycholesterols formed expanded monolayers, with lift-offs from baseline 22-26 Angstrom(2)/molecule larger than CH, suggesting interfacial tilting; furthermore, in binary mixtures, they condensed POPC monolayers less than CH, In contrast, the side chain hydroxylated CHs were oriented horizontally in the interface at large molecular areas, and became vertical below 140 Angstrom(2)/molecule with the side chain-OH rather than 3-OH group anchored in the subphase, as evidenced by low collapse pressures and smaller molecular areas than CH. Both side chain hydrocholesterols expanded POPC monolayers at molar ratios <30%, but induced condensation with higher ratios, suggesting that OH-acyl chain (POPC) repulsion is superceded at higher mole fractions by lateral phase separation and intersteroidal H-bonding. These studies predict that fluorocholesterols should exhibit intramembrane spatial occupancy nearly identical to CH, whereas nucleus and especially side chain hydroxycholesterols will perturb membrane lipid packing notably.

a; bile-acids; Biochemistry & Molecular Biology; condensation; enzyme-catalyzed oxidation; isotherm; monolayers; orientation; orphan nuclear receptor; phosphatidylcholine; phosphatidylcholines; reductase-activity; side-chain; spectroscopic imaging; sterol synthesis; surface balance; surface potential

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Journal Article or Conference Abstract Publication

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