Josefine Eilsø Nielsen1, Victoria Ariel Bjørnestad1, Vitaliy Pipich2, Håvard Jenssen3, Reidar Lund4. 1. Department of Chemistry, University of Oslo, Postboks 1033 Blindern, 0315 Oslo, Norway. 2. Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, 85747 Garching, Germany. 3. Department of Science and Environment, Roskilde University, Universitetsvej 1, Roskilde 4000, Denmark. 4. Department of Chemistry, University of Oslo, Postboks 1033 Blindern, 0315 Oslo, Norway. Electronic address: reidar.lund@kjemi.uio.no.
Abstract
HYPOTHESIS: Most textbook models for antimicrobial peptides (AMP) mode of action are focused on structural effects and pore formation in lipid membranes, while these deformations have been shown to require high concentrations of peptide bound to the membrane. Even insertion of low amounts of peptides in the membrane is hypothesized to affect the transmembrane transport of lipids, which may play a key role in the peptide effect on membranes. EXPERIMENTS: Here we combine state-of-the-art small angle X-ray/neutron scattering (SAXS/SANS) techniques to systematically study the effect of a broad selection of natural AMPs on lipid membranes. Our approach enables us to relate the structural interactions, effects on lipid exchange processes, and thermodynamic parameters, directly in the same model system. FINDINGS: The studied peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all cause a general acceleration of essential lipid transport processes, without necessarily altering the overall structure of the lipid membranes or creating organized pore-like structures. We observe rapid scrambling of the lipid composition associated with enhanced lipid transport which may trigger lethal signaling processes and enhance ion transport. The reported membrane effects provide a plausible canonical mechanism of AMP-membrane interaction and can reconcile many of the previously observed effects of AMPs on bacterial membranes.
HYPOTHESIS: Most textbook models for antimicrobial peptides (AMP) mode of action are focused on structural effects and pore formation in lipid membranes, while these deformations have been shown to require high concentrations of peptide bound to the membrane. Even insertion of low amounts of peptides in the membrane is hypothesized to affect the transmembrane transport of lipids, which may play a key role in the peptide effect on membranes. EXPERIMENTS: Here we combine state-of-the-art small angle X-ray/neutron scattering (SAXS/SANS) techniques to systematically study the effect of a broad selection of natural AMPs on lipid membranes. Our approach enables us to relate the structural interactions, effects on lipid exchange processes, and thermodynamic parameters, directly in the same model system. FINDINGS: The studied peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all cause a general acceleration of essential lipid transport processes, without necessarily altering the overall structure of the lipid membranes or creating organized pore-like structures. We observe rapid scrambling of the lipid composition associated with enhanced lipid transport which may trigger lethal signaling processes and enhance ion transport. The reported membrane effects provide a plausible canonical mechanism of AMP-membrane interaction and can reconcile many of the previously observed effects of AMPs on bacterial membranes.
Authors: Aaron B Benjamin; Madeleine G Moule; Maruti K Didwania; Jonathan Hardy; Panatda Saenkham-Huntsinger; Preeti Sule; Josefine Eilsø Nielsen; Jennifer S Lin; Christopher H Contag; Annelise E Barron; Jeffrey D Cirillo Journal: Microbiol Spectr Date: 2022-04-25
Authors: Huong T Kratochvil; Robert W Newberry; Bruk Mensa; Marco Mravic; William F DeGrado Journal: Faraday Discuss Date: 2021-12-24 Impact factor: 4.394