HYDROPHOBIC ALKYL HEADGROUPS STRONGLY PROMOTE MEMBRANE CURVATURE AND VIOLATE THE HEADGROUP VOLUME CORRELATION DUE TO HEADGROUP INSERTION

The ability of lipid aggregates to form planar bilayers, rather than highly curved micellar or inverted structures, is dependent on the relative geometries of the headgroup and hydrocarbon regions. The headgroup volume approach to lipid structure provided a quantitative link between a lipid's headgroup size and its ability to promote curved, inverted hexagonal (HII) structures in a phosphatidylethanolamine (PtdEtn) matrix [Lee et al. (1993) Biophys. J. 65, 1429−1432]. Phosphatidylalkanols (PtdAlks) are shown here to promote curvature with a potency that far exceeds and a chain length dependence contrary to the expectations of the headgroup volume approach, suggestive of an atypical alkyl “headgroup” conformation. A homologous series of 3-substituted triacylglycerols (TAGs), for which 3-acyl “headgroup” insertion is established, exhibits a chain length dependence similar to the PtdAlks, evidence that the deviation is of common origin. The potency of the TAGs to promote curvature is unprecedented, and the o...