EFFECTS OF ALCOHOLS ON THE PHASE-TRANSITION TEMPERATURES OF MIXED-CHAIN PHOSPHATIDYLCHOLINES

The biphasic effect of ethanol on the main phase transition temperatur e (T-m) of identical-chain phosphatidylcholines (PCs) in excess H2O is now well known. This biphasic effect can be attributed to the transfo rmation of the lipid bilayer, induced by high concentrations of ethano l, from the partially interdigitated L(beta), phase to the fully inter digitated L(beta I) phase at T < T-m. The basic packing unit of the L( beta I) phase has been identified recently as a binary mixture of PC/e thanol at the molar ratio of 1:2. The ethanol effect on mixed-chain PC s, however, is not known. We have thus in this study investigated the alcohol effects on the T-m of mixed-chain PCs with different Delta C v alues, where Delta C is the effective acyl chain length difference bet ween the sn-1 and sn-2 acyl chains. Initially, molecular mechanics (MM ) simulations are employed to calculate the steric energies associated with a homologous series of mixed-chain PCs packed in the partially a nd the fully interdigitated L(beta I) motifs. Based on the energetics, the preference of each mixed-chain PC for packing between these two d ifferent motifs can be estimated. Guided by MM results, high-resolutio n differential scanning calorimetry is subsequently employed to determ ine the T-m values for aqueous lipid dispersions prepared individually from a series of mixed-chain PCs (Delta C = 0.5-6.5 C-C bond lengths) in the presence of various concentrations of ethanol. Results indicat e that aqueous dispersions prepared from mixed-chain PCs with a Delta C value of less than 4 exhibit a biphasic profile in the plot of T-m v ersus ethanol concentration. In contrast, highly asymmetric PCs (Delta C > 4) do not exhibit such biphasic behavior. In the presence of a lo nger chain n-alcohol, however, aqueous dispersions of highly asymmetri c C(12):C(20)PC (Delta C = 6.5) do show such biphasic behavior against ethanol. Our results suggest that the Delta C region in a highly asym metric PC packed in the L(beta I) phase is most likely the binding sit e for n-alcohol.