Effects of short-chain alcohols on the phase behavior and interdigitation of phosphatidylcholine bilayer membranes.

Solute effects on the polymorphism and phase transitions in the suspensions of dipalmitoylphosphatidylcholine (DPPC) were studied by means of carboxyfluorescein (CF) and phosphatidylethanolamine rhodamine (PERho) fluorescence, differential scanning calorimetry, and X-ray diffraction. Specifically, the shifts of the lipid chain-melting phase transition, pretransition and subtransition temperature as a function of the bulk alcohol concentration were determined calorimetrically. The chain-melting phase transition temperature, Tm, was found to depend on the chain-length of the added alcohol: for short-chain alcohols (up to n-propanol), Tm first decreases and then increases with increasing alcohol concentration. For longer-chain alcohols, however, Tm decreases over the whole investigated alcohol concentration range. The pretransition and the subtransition temperature of DPPC both decrease monotonously (but non-linearly) with increasing alcohol concentration, but the former transition disappears at some characteristic, chain-length dependent alcohol concentration, cL beta i. This point in the solute-dependent phase diagram of DPPC is diagnostic of the complete hydrocarbon interdigitation. It was determined for a series of short-chain alcohols ranging from methanol through to 1-hexanol. A quantitative formula for the calculation of such limiting alcohol concentration is introduced. This formula relates the cL beta i values to the free energy of transfer of alcohols from the aqueous sub-phase into the DPPC sub-phase. By using the concept of an apparent chain-length this formalism can also be used for the alcohols with polar OH-groups at the second or third position on the hydrocarbon chain. Alcohol-induced hydrocarbon interdigitation in the phospholipid bilayers is thus shown to result chiefly from the solute-induced perturbation (lateral expansion) in the lipid headgroup region. Longer-chain alcohols, which balance this effect by disordering the phospholipid chains, therefore do not induce chain interdigitation.