Interbilayer lipid mixing induced by the human immunodeficiency virus type-1 fusion peptide on large unilamellar vesicles: the nature of the nonlamellar intermediates

A peptide corresponding to the 23 N-terminal amino acid residues of the hum an immunodeficiency virus type-1 (HIV-1) gp41 has the capacity to induce in tervesicular lipid mixing in large unilamellar liposomes composed of dioleo ylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE) and c holesterol (CHOL) (molar ratio, 1:1:1). Cryo-transmission electron microsco py (cryo-TEM) of diluted vesicles to which peptides has been externally add ed reveals a morphology that is compatible with the formation of nonlamella r lipidic aggregates during the time-course of lipid mixing. P-31-nuclear m agnetic resonance and 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMADPH) steady-state anisotropy data at equilibrium indicate that the pept ide is able to modulate the lipid polymorphism in pelletted membranes by: ( i) promoting the thermotropic formation of inverted phases; and (ii) drivin g the lamellar-to-nonlamellar transition towards the formation of isotropic phases. Therefore, our combined morphological and spectroscopic data revea l the existence of a direct correlation between the ability of the external ly added peptide to induce lipid-mixing in dilute liposome samples and its capacity to modulate lipid polymorphism in stacked bilayers. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.