MOLECULAR-ORGANIZATION AND STABILITY OF HYDRATED DISPERSIONS OF HEADGROUP-MODIFIED PHOSPHATIDYLETHANOLAMINE ANALOGS

Measurements of the thermotropic behavior of various headgroup-modified analogues of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) and of the ion-triggered destabilization of unilamellar vesicles containing these species have been correlated with X-ray diffraction measurements of the organization of hydrated dispersions of these analogues in the absence and presence of dodecane. The hexagonal II lattice repeat dimension dBAR(hex) for dodecane-supplemented dispersions, which reflects the optimal or "spontaneous" radius of surface curvature of the phospholipid component, is increased relative to POPE for most analogues with N-alkyl substituents or increased amino-to-phosphate group separations. Interestingly, however, POPE analogues that are alkylated on C-1 or C-2 of the ethanolamine group show smaller dBAR(hex) values (and hence smaller spontaneous radii of surface curvature) than does POPE itself, despite the greater steric bulk of their headgroups. The lamellar-to-hexagonal 11 transition temperatures of the various POPE analogues and their abilities to promote contact-dependent vesicle destabilization both show strong correlations with the analogues' measured dBAR(hex) values (and hence with their spontaneous radii of curvature). The uniformity of these correlations over a wide range of headgroup structures strongly supports, and may help to refine, recent theories which postulate that the spontaneous surface curvature of a lipid or lipid mixture is a central, quantitative determinant of its tendency to adopt nonlamellar phases and to undergo contact-dependent bilayer destabilization.