Nano-mechanical in-process monitoring of antimicrobial poration in model phospholipid bilayers

Host defense or antimicrobial peptides (AMPs) are a major part of the innate immune system of all cellular organisms, from bacteria to humans. The peptides are typically broad-spectrum antibiotics that recognize and target microbial membranes, including bacterial, fungal and viral. Unlike conventional antibiotics, AMPs do not differentiate between mature and growing bacteria, or between different types of bacteria, Gram positive or Gram negative, but destroy all. Partly, this is because microbial cell walls as well as their membranes, phospholipid bilayers, are anionic, which allows these cationic peptides to bind to microbial cells. Partly, because AMPs fold into amphipathic conformations of a-helices or b-sheets, which allows them to intercalate in the hydrophobic interfaces of microbial phospholipid bilayers whereupon they assemble into membranedisrupting pores and lesions causing cell lysis. Given that widespread resistance against them has yet to emerge, it is not surprising that AMPs are being considered as next-generation antimicrobial agents in the post-antibiotic era. Similar to antibiotics, AMPs can engage with intracellular targets or disrupt processes that are crucial to the viability of microorganisms (protein, DNA, or cell wall syntheses). However, microbial membranes constitute themain and rst line of attack for AMPs. This is the hallmark of their activity. Consequently, it is the interactions of these peptides with microbial phospholipid bilayers, their nature and extent that specify mechanisms of membrane disintegration. There appears to be several factors to consider that range from amino-acid compositions to inoculum effects. Yet, conformational responses to lipid binding remain