Morphological behavior of acidic and neutral liposomes induced by basic amphiphilic alpha-helical peptides with systematically varied hydrophobic-hydrophilic balance

Lipid-peptide interaction has been investigated using cationic amphiphilic a-helical peptides and systematically varying their hydrophobic-hydrophilic balance (HHB). The influence of the peptides on neutral and acidic liposom es was examined by 1) Trp fluorescence quenched by brominated phospholipid, 2) membrane-clearing ability, 3) size determination of liposomes by dynami c light scattering, 4) morphological observation by electron microscopy, an d 5) ability to form planar lipid bilayers from channels. The peptides exam ined consist of hydrophobic Leu and hydrophilic Lys residues with ratios 13 :5, 11:7, 9:9, 7:11, and 5:13 (abbreviated as Hels 13-5, 11-7, 9-9, 7-11, a nd 5-13, respectively; Kiyota, T., S. Lee, and G. Sugihara. 1996. Biochemis try. 35:13196-13204). The most hydrophobic peptide (Hel 13-5) induced a twi sted ribbon-like fibril structure for egg PC liposomes. In a 3/1 (egg PC/eg g PG) lipid mixture, Hel 13-5 addition caused fusion of the liposomes. Hel 13-5 formed ion channels in neutral lipid bilayer (egg PE/egg PC = 7/3) at low peptide concentrations, but not in an acidic bilayer (egg PE/brain PS = 7/3), The peptides with hydrophobicity less than Her 13-5 (Hels 11-7 and H el 9-9) were able to partially immerse their hydrophobic part of the amphip hilic helix in lipid bilayers and fragment liposome to small bicelles or mi celles, and then the bicelles aggregated to form a larger assembly. Peptide s Hel 11-7 and Hel 9-9 each formed strong ion channels. Peptides (Hel 7-11 and Hel 5-13) with a more hydrophilic HHB interacted with an acidic lipid b ilayer by charge interaction, in which the former immerses the hydrophobic part in lipid bilayer, and the latter did not immerse, and formed large ass emblies by aggregation of original liposomes. The present study clearly sho wed that hydrophobic-hydrophilic balance of a peptide is a crucial factor i n understanding lipid-peptide interactions.