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 h ighly curved micellar or inverted structures, is dependent on the rela tive geometries of the headgroup and hydrocarbon regions. The headgrou p volume approach to lipid structure provided a quantitative link betw een a lipid's headgroup size and its ability to promote curved, invert ed hexagonal (H-II) structures in a phosphatidylethanolamine (PtdEtn) matrix [Lee et al. (1993) Biophys. J. 65, 1429-1432]. Phosphatidylalka nols (PtdAlks) are shown here to promote curvature with a potency that far exceeds and a chain length dependence contrary to the expectation s of the headgroup volume approach, suggestive of an atypical alkyl '' headgroup'' conformation. A homologous series of 3-substituted triacyl glycerols (TAGs), for which 3-acyl ''headgroup'' insertion is establis hed, exhibits a chain length dependence similar to the PtdAlks, eviden ce that the deviation is of common origin. The potency of the TAGs to promote curvature is unprecedented, and the onset of saturation, which parallels the dramatic promotion of curvature, occurs at mole fractio ns as low as 0.0025. The potency of the PtdAlks or TAGs to promote cur vature exceeds that of all mammalian phospholipids examined. Thermodyn amic analysis implicates the enthalpic curvature stress imparted upon the membrane matrix as the dominant energetic factor. The imparted str ess ranges from -930 J mol(-1) for phosphatidylcholine to +7.5 kJ mol( -1) for 3-palmitoyl TAG. The results affirm the geometric consideratio ns of membrane structure and indicate that alkyl headgroups tend to in sert into the bilayer and increase the enthalpic curvature stress with in the membrane.