Interactions of antibiotic peptides with lipid membranes

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Interactions of several antibiotic peptides with lipid membranes were investigated by using spectroscopic and thermal techniques to elucidate their action mechanisms. We found the followings. 1. Hydroprhobic hypelein and trichopolyn permeabilize lecithin membranes. Both membrane affinity and membrane-perturbing activity of hypelcin were three times larger than those of trichopolyn. This finding corresponds well to a stronger hemolytic activity of hypelcin. Our FTIR-ATR study revealed that both peptides conform to helices in membranes, deeply penetrating their hydrophobic region, disrupting their lipid orientation to permeabilize them. Correspondingly, the membrane phase transition disappears. 2. Amphilphilic magainins specifically interact with acidic lipid bilayers, forming amphiphilic helices to permeabilize the membranes. Electrostatic interactions are important for the membrane binding. A fluorescence study using tryptophan-substituted analogs shows that magainins lay in a shallow region of the membranes in an aggregated form. Furthermore, a truncated derivative shows a similar activity compared with the parent peptide, suggesting that the C-terminal five residues are unnecessary for the activity. 3. Tachyplesin, having an amphiphilic sheet structure, specifically and strongly bind to acidic phospholipids, enhancing the membrane permeability. Further addition of the peptide aggregates, fuse, and micellize 100 nm-sized liposomes, forming small particles of 10-20 nm in diameter. Charge neutralization seems to be important for the small particle formation. Bilayers in the gel state are more susceptible to these morphological changes than those in the fluid state. The unique tryptophan residue is located in a hydrophobic region near the membrane surface.