ADJUVANT LIPOPEPTIDE INTERACTION WITH MODEL MEMBRANES

The cationic lipohexapeptide Pam(3)Cys-Ser-(Lys)(4) is a synthetic mod el for the triacylated N-terminal part of bacterial lipoproteins, and it is used as an adjuvant and macrophage activator. The amphiphilic li popeptide was injected below a phosphatidylserine monolayer at the air -water interface. It interacted with the interface, as seen by a decre ase in the surface potential (Delta V), and it was inserted in the mon olayer, until surface charge neutralization was reached, as seen by th e parallel increases of Delta V and of the surface pressure. No insert ion occurred above 29 mN/m. The interaction kinetics was sensitive to ionic strength and to the nature of acidic phospholipids and of their acyl chains, but the final equilibrium was independent of these factor s. Addition of the lipopeptide to large unilamellar vesicles (LUVs) in duced their aggregation, and an exchange of lipids between fluorophor- labelled and non-labelled LUVs. However, no fusion was observed, just as reported for polylysine. The lipopeptide strongly inhibited calcium -induced fusion of PS LUVs, in contrast to the published effect of pol ylysine. This was probably due to inhibition of calcium fixation on li posomes, since it was observed that the lipopeptide efficiently displa ced Ca-45(2+) from a PS monolayer. In addition, a phospholipid segrega tion was observed in SUVs for a few ten micromolar of the lipopeptide. (C) 1998 Elsevier Science B.V.