A Bioinspired Mastoparan Exhibits Concentration-Dependent Anti-Bacterial Activity via Membrane Disruption.

Antimicrobial peptides are widely investigated in the literature, but their mechanism of action and effects on lipid membranes are not completely understood from a physicochemical perspective. In this study, we employed a bioinspired mastoparan from wasp venom, mast-MO, and characterized its interactions with model lipid membranes, either as a supported lipid bilayer or as free-standing vesicles in solution. An array of complementary physicochemical characterization techniques was employed to study the surface activity of the peptide alone and how its adsorption affects lipid membrane properties in terms of lateral organization and integrity. We found that peptide action is related to its intrinsic surface activity, resulting in disrupted lipid packing of supported membranes and vesicles via a concentration-dependent mechanism. Changing solution conditions, e.g., ionic strength and pH, altered the electrostatic interactions between the membrane and mast-MO, resulting in less significant adsorption. This mechanism of action was also validated in vitro for Gram-negative E. coli bacteria, demonstrating rapid action (within 15 min) and potent antimicrobial activity. These results provide new information on the molecular effects of mastoparan's interactions with membranes.