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

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:582

Article

Nielsen, Josefine Eilso¹  Bjornestad, Victoria Ariel¹  Pipich, Vitaliy²  Jenssen, Havard³  Lund, Reidar¹ 

[1] Univ Oslo, Dept Chem, Postboks 1033, N-0315 Oslo, Norway

[2] Forschungszentrum Julich, Julich Ctr Neutron Sci JCNS, Heinz Maier Leibnitz Zentrum MLZ, D-85747 Garching, Germany

[3] Roskilde Univ, Dept Sci & Environm, Univ Vej 1, DK-4000 Roskilde, Denmark

关键词: Antimicrobial peptides;    Lipid membranes;    Lipid transport;    Neutron scattering;    X-ray scattering;   

DOI  :  10.1016/j.jcis.2020.08.094

来源: Elsevier

【 摘 要 】

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. (C) 2020 The Author(s). Published by Elsevier Inc.

【 授权许可】

Free