Simultaneously measuring the effect of Antimicrobial Peptides on Ion Conduction and Structure of Model Membranes with TR-SAXS

Antimicrobial peptides (AMPs) are promising antibiotic candidates, acting primarily on bacterial membranes. While their mode of action remains debated, transmembrane pore formation is often suggested. In a recent preprint, we demonstrated that AMPs permeabilize membranes via transient aqueous pores rather than stable structural pores, likely due to increased lipid flip-flop rates. Time-resolved SAXS (TR-SAXS) experiments at ID02 showed rapid ion equilibration across lipid membranes within tens of milliseconds (Fig. 1E, 1F). Building on this, we aim to investigate different salts (K+, Br-, Mg2+, Ca2+) and peptide:lipid ratios to develop a general permeabilization model. With strong preliminary data and established analytical models, we propose further TR-SAXS experiments to refine our understanding of AMP-induced permeabilization, advancing their potential as novel antibiotics.