Penetration of the antimicrobial peptide dicynthaurin into phospholipid monolayers at the liquid-air interface

This work focuses on the adsorption kinetics of dicynthourin with lipid monolayers, the effect of peptide adsorption on the structure of the lipid condensed chain lattice, peptide orientation and secondary structure in the adsorbed state. The studies with DPPG as model system revealed strong adsorption and massive incorporation of the peptide into the monoloyer. Infrared reflection absorption spectroscopy (IRRAS) experiments showed that the secondary structure of the peptide is maintained upon adsorption. Speculor X-ray reflectivity showed the destabilization of the condensed phase of the pure lipid monolayer and revealed a tilted orientation of the long axis of the peptide helix of about 40 degrees from the surface normal. Incorporation of the peptide was found to be pressure dependent, and at high pressure a "squeeze-out" was observed; however, the peptide remained localized to the interface, as suggested by infrared data. These findings were supported by optical fluorescence microscopy measurements which showed the squeeze-out of the peptide on water, but not under physiological conditions. The results suggest that dicynthourin is able to adsorb to the phosphotidylglycerol-rich inner cytoplasmic membrane of bacteria and alter membrane integrity. To identify and interact with membrane motifs that are characteristic of microbes, but which are absent in eukaryotic cells, might be an intrinsic ability of peptide antibiotics.