A DSC and FTIR spectroscopic study of the effects of the epimeric 4,6-cholestadien-3-ols and 4,6-cholestadien-3-one on the thermotropic phase behaviour and organization of dipalmitoylphosphatidylcholine bilayer membranes

We present the results of a comparative differential calorimetric and Fourier transform infrared spectroscopic study of the effect of cholesterol and five analogues on the thermotropic phase behaviour and organization of dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ in both the nature and stereochemistry of the polar head group at C3 (beta OH, alpha OH or C=O) and in the position(s) of the double bond(s). In the Delta(5) sterols/steroid series, the concentration of these compounds required to abolish the DPPC pretransition, inversely related to their relative ability to disorder gel state DPPC bilayers, decreases markedly in the order beta OH> alpha OH > C=O. However, in the Delta(4,6) series, these concentrations are similar, regardless of polar head group chemical structure. Similarly, the residual enthalpy of the DPPC main phase transition at 50 mol% sterol/steroid, which is inversely related to the miscibility of these compounds in the DPPC bilayer, also increases in the order beta OH > alpha OH > C=O, but this effect is attenuated in the Delta(4,6) series. In the two pairs of sterol epimers, the Delta(4,6) compounds exhibit a greater decrease in the temperature and enthalpy of both the pretransition and the main phase transition, whereas the opposite result is observed in the ketosteroid pair. Similarly, the ability of these compounds to order the DPPC hydrocarbon chains decreases in the order beta OH > alpha OH > C=O in both series of compounds, but in the two pairs of sterol epimers, hydrocarbon chain ordering is greater for the Delta(5) than the Delta(4,6) sterols, whereas the opposite is the case for the steroid pair. Thus, the characteristic effects of sterols/steroids on fluid lipid bilayers are optimal when an OH group rather than C=O group is present at C3, and when this OH group is in the equatorial orientation. We suggest that the presence of keto-enol tautomerism in the conjugated Delta(4,6) ketosteroid may provide additional H-bonding opportunities to adjacent DPPC molecules in the bilayer, which results in more cholesterol-like effects. (C) 2014 Elsevier Ireland Ltd. All rights reserved.