Interactions of basic amphiphilic peptides with dimyristoylphosphatidylcholine small unilamellar vesicles: optical, NMR, and electron microscopy studies and conformational calculations.

The interactions of DMPC small unilamellar vesicles with four amphiphilic polypeptides [(LKKL)n, (LRRL)n, (LKKL)4, and (YKKY)n] have been investigated by circular and infrared dichroism, turbidimetry, electron microscopy, and fluorescence, 1H, and 31P nuclear magnetic resonance spectroscopy. The main results obtained are the following: (1) Well-defined complexes are formed by the association of one amino acid residue with approximately two lipid molecules. (2) In the presence of polypeptides fusions are observed between SUVs when the molar ratio p is less than 0.05, and a clearance effect is observed when p is higher than 0.05. (3) The anchoring sites of the polypeptides on DMPC molecules are the negative phosphate groups through electrostatic interactions with the terminal NH3+ of lysine residues. (4) The polypeptides adopt an alpha-helical conformation with their axis parallel to the membrane surface. The hydrophobic part of the amphiphilic alpha helix can penetrate the outer lipid leaflet down to the C5 position. (5) Choline methyl groups are not involved in the interactions between lipid molecules and amino acid residues. (6) Phosphorus atom mobility around the P-O-glycerol bond is strongly reduced whereas that of methylene groups is progressively weakened when going up from C13 to C1. Finally, using modeling and energy calculations a model of possible Ac(LKKL)4NHEt-DMPC SUV complexes is presented.