Modulating the structure and interactions of lipid-peptide complexes by varying membrane composition and solution conditions

The interactions between membranes and peptides depend on the detailed peptides' structure, lipid composition, and membrane structure. Here, we study the interaction of lipid membrane with a short peptide, which under certain conditions may penetrate cells. Using solution X-ray scattering, we investigated the structures that form when mixing the peptide Ac-Gly-Phe-d-Phe-Arg-Trp-Gly- NH₂ with a variety of lipid membranes. We studied how lipid mixtures, containing lipids with different properties, control the interactions and, thereby the structures of the resulting lipid-peptide complexes. We found that below a critical concentration the peptides associate with the lipid bilayers and thin the membranes. For a fraction of charged lipids below 0.75 and above some critical peptide concentration, the peptide can bridge like-charged membranes. Moreover, the peptide can charge zwitterionic DOPC membranes, or convert the inverted hexagonal phase of the DOPE lipid into a multilamellar phase. We attribute these observations to a balance between hydrophobic, electrostatic, entropic, and steric effects, associated with the specific structures of the peptide and membranes. The two short hydrophobic moieties of the peptide favor the hydrophobic part of the membranes, whereas its charged amino acid (Arg), situated in the middle, prefers the aqueous environment. The membrane charge density, spontaneous curvature, lipid packing parameter, as well as solution conditions were carefully studied and allow a comprehensive understanding of these assemblies under a consistent framework.