Beyond structural models for the mode of action: How natural antimicrobial peptides affect lipid transport

Josefine Eilsø Nielsen, Victoria Ariel Bjørnestad, Vitaliy Pipich, Håvard Jenssen, Reidar Lund*

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.
OriginalsprogEngelsk
TidsskriftJournal of Colloid and Interface Science
Vol/bind582
Udgave nummerPart b
Sider (fra-til)793-802
Antal sider10
ISSN0021-9797
DOI
StatusUdgivet - 15 jan. 2021

Emneord

  • Antimicrobial peptides
  • Lipid membranes
  • Lipid transport
  • Neutron scattering
  • X-ray scattering

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