COMPARATIVE DIFFERENTIAL SCANNING CALORIMETRIC AND FTIR AND P-31-NMR SPECTROSCOPIC STUDIES OF THE EFFECTS OF CHOLESTEROL AND ANDROSTENOL ONTHE THERMOTROPIC PHASE-BEHAVIOR AND ORGANIZATION OF PHOSPHATIDYLCHOLINE BILAYERS

We have investigated the comparative effects of the incorporation of i ncreasing quantities of androstenol and cholesterol on the thermotropi c phase behavior of aqueous dispersions of members of a homologous ser ies of linear saturated diacyl PCs1 using high sensitivity DSC. We hav e also employed FTIR and P-31-NMR spectroscopy to study the comparativ e effects of androstenol and cholesterol incorporation on the organiza tion of the host PC bilayer in both the gel and liquid-crystalline sta tes. The effects of androstenol and cholesterol incorporation on the t hermotropic phase behavior of shorter chain PCs like 14:0 PC are gener ally similar but not identical. The incorporation of either sterol pro gressively decreases the temperature and enthalpy, but not the coopera tivity, of the pretransition and completely abolishes it at sterol con centrations above 5 mol%. Moreover, at sterol concentrations of 1 to 2 0-25 mol%, both androstenol and cholesterol incorporation produce DSC endotherms consisting of superimposed sharp and broad components, the former due to the hydrocarbon chain melting of sterol-poor and the lat ter to the melting of sterol-rich 14:0 PC domains. The temperature and cooperativity of the sharp component are reduced slightly with increa sing concentration of androstenol or cholesterol, and the enthalpy of the sharp component decreases progressively and becomes zero at 20-25 mol% sterol. As well, at cholesterol or androstenol concentrations abo ve 20-25 mol%, the enthalpy of the broad component also decreases line arly with increasing sterol incorporation and becomes zero at sterol l evels of about 50 mol%. However, whereas cholesterol incorporation pro gressively increases the temperature of the broad component of the DSC endotherm, androstenol incorporation decreases the temperature of thi s component. in contrast, the effects of androstenol and cholesterol i ncorporation on the thermotropic phase behavior of the intermediate an d longer chain PCs studied here are considerably different. Although t he incorporation of cholesterol increases the main phase transition te mperature of 16:0 PC slightly and decreases the phase transition of 18 :0 PC and 21:0 PC, androstenol incorporation decreases the main phase transition temperatures of all three PCs rather markedly. Moreover, an drostenol is less effective in reducing the enthalpy and cooperativity of the broad component of the DSC endotherm of 16:0 PC and especially 18:0 PC bilayers in comparison to cholesterol. Androstenol incorporat ion (>5 mol%) also results in the appearance of a second, low temperat ure endotherm in the DSC traces of the intermediate and longer chain P C dispersions that is not observed in similar cholesterol/PC dispersio ns. FTIR and P-31-NMR results suggest that this endotherm arises from a temperature-induced dissolution of androstenol in the gel phase PC b ilayers. This second endotherm occurs at lower androstenol concentrati ons and increases in area at a given androstenol level as the chain le ngth of the host PC bilayer increases. We ascribe the increasing immis cibility of androstenol in both the gel and liquid-crystalline states of PC bilayers of increasing thickness to an increasing degree of hydr ophobic mismatch between the androstenol molecule and the host phospho lipid bilayer.