The molecular organization of asymmetric lipid bilayers and lipid-peptide complexes.

Oriented fatty acid bilayers with asymmetric distributions of lipid head group types, hydrocarbon chain lengths, and associated polypeptides have been analyzed by a combined use of high resolution electron microscopy and X-ray diffraction techniques. The exclusion of fixatives, stains, and embedding materials has made it possible to relate unequivocally microscopic images to molecular composition. The ultrastructure of asymmetric bilayers has been determined by a novel analysis in which one half of the bilayer serves as a structural reference for the entire bilayer. Absolute electron density profiles at 7 A resolution have been computed for bilayers formed from long and short chain length lipids either segregated to opposite sides or mixed together in both sides of the bilayer. The data indicate that the two lipids self organize in a specific paired configuration. Detailed analysis of bilayers associated with poly-L-lysine shows that although this hydrophilic peptide resides near the lipid head group region, its presence alters the arrangement of the bilayer hydrocarbon chains.