The lipid bilayer as a ‘solvent’ for small hydrophobic molecules

Abstract

THE cell membrane is viewed at present as a two-dimensional solution in which the lipid bilayer acts as a viscous ‘solvent’ for oriented integral proteins¹. Accepting this model as a working hypothesis, questions arise as to the nature of the hydrophobic interior of the bilayer and what rules proteins, lipoproteins, or polypeptides obey in interacting with it. The simplest hypothesis for the interior is that it is equivalent to a bulk alkyl solvent (albeit a very thin one). If this hypothesis is correct, the enthalpy of transfer (ΔH) of a solute molecule (for example, an alkane) from a bulk alkyl solvent to the bilayer interior should be small. That is, the solute-solvent interaction energy should be about the same in the bilayer as in the bulk alkyl. I have examined this hypothesis experimentally by measuring the solubility of n-hexadecane in planar bilayer membranes formed from glycerol-1-monooleate (1-GMO). The acyl chain of 1-GMO is approximately equivalent to 1-heptadecene. The enthalpy of transfer of n-hexadecane from pure liquid into 1-heptadecene can be estimated from solubility parameter theory² to be only a few calories per mol. Thus, the mixing of n-hexadecane in the bilayer interior should be nearly athermal: I have found, however, that δH is orders of magnitude larger than expected. This result has important implications for understanding the bilayer as a two-dimensional solution.