biostudies-literatureSani MAAustralian Research Council1058-1067https://www.ebi.ac.uk/biostudies/studies/S-EPMC10111263biostudies-literatureUnknown122(6)Antimicrobial peptides are an important class of membrane-active peptides that can provide alternatives or complements to classic antibiotics. Among the many classes of AMPs, the histidine-rich family is of particular interest since they may induce pH-sensitive interactions with cell membranes. The AMP caerin 1.1 (Cae-1), from Australian tree frogs, has three histidine residues, and thus we studied the pH dependence of its interactions with model cell membranes. Using NMR spectroscopy and molecular dynamics simulations, we showed that Cae-1 induced greater perturbation of the lipid dynamics and water penetrations within the membrane interior in an acidic environment compared with physiological conditions. Using ³¹P solid-state NMR, the packing, chemical environment, and dynamicsBiophysical journalThe membrane activity of the antimicrobial peptide caerin 1.1 is pH dependent.PMC10111263DP190101506LE160100120DP210101792Sani MASeparovic FLe Brun APRajput SAttard TfalseThe membrane activity of the antimicrobial peptide caerin 1.1 is pH dependent.Antimicrobial peptides are an important class of membrane-active peptides that can provide alternatives or complements to classic antibiotics. Among the many classes of AMPs, the histidine-rich family is of particular interest since they may induce pH-sensitive interactions with cell membranes. The AMP caerin 1.1 (Cae-1), from Australian tree frogs, has three histidine residues, and thus we studied the pH dependence of its interactions with model cell membranes. Using NMR spectroscopy and molecular dynamics simulations, we showed that Cae-1 induced greater perturbation of the lipid dynamics and water penetrations within the membrane interior in an acidic environment compared with physiological conditions. Using ³¹P solid-state NMR, the packing, chemical environment, and dynamics2023-01-01T00:00:00Z2023 Mar2025-04-21T19:07:06.919Z2025-04-05T17:29:39.037ZS-EPMC101112633668034310.1016/j.bpj.2023.01.021