The interaction of antimicrobial peptides with membranes.

The interaction of antimicrobial peptides (AMPs) with biological membranes is in the focus of research since several years, and the most important features and modes of action of AMPs are described in this review. Different model systems can be used to understand such interactions on a molecular level. As a special example, we use 2D and 3D model membranes to investigate the interaction of the natural cyclic (Ar-1) and the synthetic linear molecule arenicin with selected amphiphiles and phospholipids. A panoply of sophisticated methods has been used to analyze these interactions on a molecular level. As a general trend, one observes that cationic antimicrobial peptides do not interact with cationic amphiphiles due to electrostatic repulsion, whereas with non-ionic amphiphiles, the peptide interacts only with aggregated systems and not with monomers. The interaction is weak (hydrophobic interaction) and requires an aggregated state with a large surface (cylindrical micelles). Anionic amphiphiles (as monomers or micelles) exhibit strong electrostatic interactions with the AMPs leading to changes in the peptide conformation. Both types of peptides interact strongly with anionic phospholipid monolayers with a preference for fluid layers. The interaction with a zwitterionic layer is almost absent for the linear derivative but measurable for the cyclic arenicin Ar-1. This is in accordance with biological experiments showing that Ar-1 forms well defined stable pores in phospholipid and lipopolysaccharide (LPS) membranes (cytotoxicity). The synthetic linear arenicin, which is less cytotoxic, does not affect the mammalian lipids to such an extent. The interaction of arenicin with bacterial membrane lipids is dominated by hydrogen bonding together with electrostatic and hydrophobic interactions.