Physicochemical Characterization of Daptomycin Interaction with Negatively Charged Lipid Membranes

[Image: see text] Daptomycin is known as an effective antibiotic lipopeptide which shows activity against the number of Gram-positive pathogens. Its primary target is the bacterial cell membrane. However, the detailed mechanism of daptomycin action is still subject to debate. In this paper, we have investigated the interactions between lipopeptide and model lipid films composed of negatively charged phosphatidylglycerols and cardiolipin. In order to evaluate the effect of daptomycin on the molecular organization and the properties of lipid assemblies, we have used surface pressure measurements and electrochemical methods combined with atomic force microscopy, quartz crystal microbalance, and surface-enhanced infrared absorption spectroscopy. Our results indicate that daptomycin interaction with the lipid membrane is complex. It involves daptomycin aggregation and partial insertion, which in turn affect the charge distribution on both sides of the membrane and may result in a gradient of water chemical potential. The latter can drive the flux of water across the membrane.