ROLE OF INTERACTIONS AT THE LIPID-WATER INTERFACE FOR DOMAIN FORMATION

The lipid-water interface is critical for the packing of lipid molecul es in membranes, We have demonstrated that lateral phase separation in membranes can be driven by electrostatic interactions such as those i nvolving charged lipid species and oppositely charged peptides, in add ition to hydration effects at the lipid-water interface. By using nucl ear magnetic resonance (NMR), circular dichroism and fluorescence spec troscopy we have shown that binding of a 21-amino acid peptide contain ing six positively charged arginine residues to mixed phosphatidylchol ine (PC)/phosphatidylglycerol (PG) membranes results in a conformation al change in the peptide from a random coil to a helical structure and causes the formation of domains of negatively charged PG. Binding of the peptide to PG membranes disorders the lipid hydrocarbon chains. Th e strength of lipid-peptide binding at the interface, the conformation al change in the peptide, and domain formation with the negatively cha rged lipid are coupled energetically. The lipid-peptide association co nstant is lower for membranes containing 20 mol% Po in PC/PG mixtures than for 100% PG membranes. We suggest that one of the factors that lo wer the association constant in PC/PG membranes is entropic energy of formation of PG domains. Besides electrostatic interactions, hydration of lipids is important for domain formation. We have shown that dipal mitoylphosphatidylcholine and dipalmitoylphosphatidylethanolamine sepa rate under conditions of decreased water activity. Furthermore, water activity controls lipid packing stress in the hydrocarbon core and the headgroups of membranes as demonstrated by induction of an inverse-he xagonal-to-lamellar phase transition in dioleoylphosphatidylethanolami ne. The experiments have shown that lipid-peptide and lipid-water inte ractions at the interface influence the packing of lipid hydrocarbon c hains. Consequently we predict that a change in lipid-lipid interactio n in the hydrocarbon core of the membrane, for example as a result of the introduction of polyunsaturated fatty acids, will alter lipid-solv ent and lipid-peptide interactions al the interface.