Bilayer partition coefficients of alkanols: Predicted effects of varying lipid composition

Partition coefficients of short n-alkanols between bilayers of different lipid composition (equivalently, the variation in bilayer/water partition coefficients) are calculated as a function of lipid acyl chain length and unsaturation, the strength of lipid headgroup repulsions, and the addition of cholesterol. Predictions are obtained from a statistical thermodynamic approach using a mean field lattice model identical to that used recently to calculate the lateral pressure profile in fluid bilayers. Increasing length, and particularly increasing cis-unsaturation of the acyl chains, are predicted to increase the bilayer/water partition coefficients of short-chain alkanols, whereas addition of cholesterol is predicted to have the opposite effect. The magnitude of the shifts are predicted to be significantly larger for lipids with headgroups with little or no repulsions, such as phosphatidylethanolamine, than for more strongly repulsive headgroups such as phosphatidylcholine.