Structure, Interactions, and Assembly of Membrane-Active Antimicrobial Polypeptides

Antimicrobial peptides (AMPs) are emerging as potential antibacterial drugs in the face of rapidly increasing bacterial resistance to conventional antibiotics. These peptides target the microbial membrane, and numerous models are used to describe their mechanism of action, causing cell content release and membrane disruption leading to cell death. The interaction between AMPs and target membranes is critical to their specificity and activity. However, a precise understanding of the relationship between AMP structure and their cytolytic function in a range of organisms remains elusive. The challenges in the field reside in the complex nature of AMP interactions with cell membranes, the mechanism of which varies considerably between different AMP classes. Biophysical techniques are widely used to study the influence of peptide structures and membrane properties on AMP cytolytic activity in model membrane systems and, recently, in live cells. In this review, we discuss high-resolution techniques that are employed to study the mechanism of membrane disruption and provide structural and functional insights into AMPs. Our aim is to provide a compendium of experimental and theoretical modeling approaches that can be used to characterize the folding and interactions of AMPs and synergistically advance the development of a new generation of effective antimicrobial therapeutics.