Examining the Molecular Mechanism of Antimicrobial Peptides using Neutron and X-ray Scattering Techniques
Abstract
Antimicrobial peptides (AMPs) are found in Nature as a part of the innate immune system in a wide range of species, including humans. Because of the emerging concern of widespread antibiotic resistance new antibiotics are of great importance. AMPs have attracted considerable interest, but the exact molecular mechanism of these compounds is still an object of debate. AMPs have been hypothesised to cause pore formation, membrane-solubilisation, or changes to the overall membrane structures. Here we combine small angle X-ray/neutron scattering techniques, and neutron reflectometry to systematically study the effect of a broad selection of AMPs on lipid membranes. Our results reveal a general peptide-induced acceleration of lipid transport processes, without changes to the overall membrane structure or creation of organised pores. Enhanced lipid transport can be linked with rapid scrambling of the lipid composition which may trigger lethal signalling processes, and enhance ion transport. The reported membrane effects provide a plausible canonical mechanism of AMP-membrane interaction and may reconcile previously observed effects of AMPs on bacterial membranes.List of papers
Paper I. Resolving the structural interactions between antimicrobial peptides and lipid membranes using small-angle scattering methods: the case of indolicidin. Josefine Eilsø Nielsen, Victoria Ariel Bjørnestad and Reidar Lund. Soft Matter, 2018,14, 8750-8763. DOI: 10.1039/C8SM01888J. The article is included in the thesis. Also available at: https://doi.org/10.1039/C8SM01888J |
Paper II. A biophysical study of the interactions between the antimicrobial peptide indolicidin and lipid model systems. Josefine Eilsø Nielsen, Tania Kjellerup Lind, Abdullah Lone, Yuri Gerelli, Paul Robert Hansen, Håvard Jenssen, Marité Cárdenas, Reidar Lund. Biochimica et Biophysica Acta (BBA) - Biomembranes. Vol. 1861(7), 1 July 2019, Pages 1355-1364. DOI: 10.1016/j.bbamem.2019.04.003. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.bbamem.2019.04.003 |
Paper III. 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. Journal of Colloid and Interface Science, Vol. 582, Part B, 15 January 2021, Pages 793-802. DOI: 10.1016/j.jcis.2020.08.094. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.jcis.2020.08.094 |
Paper IV. Impact of antimicrobial peptides on E. coli-mimicking lipid model membranes: correlating structural and dynamic effects using scattering methods. Josefine Eilsø Nielsen, Sylvain François Prévost, Håvard Jenssen and Reidar Lund. Faraday Discussions, 2021,232, 203-217. DOI: 10.1039/D0FD00046A. The article is included in the thesis. Also available at: https://doi.org/10.1039/D0FD00046A |
Paper V. Kinetics of lipid exchange and flip-flop in lipid bilayers with added peptides: Extracting the leaflet compositions using time-resolved small-angle neutron scattering. Published as: Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides. Josefine Eilsø Nielsen, Reidar Lund. Langmuir 2022, 38, 1, 374–384. DOI: 10.1021/acs.langmuir.1c02736. The article is included in the thesis. Also available at: https://doi.org/10.1021/acs.langmuir.1c02736 |
Paper VI. Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation. Josefine Eilsø Nielsen, Nico König, Su Yang, Maximilian W. A. Skoda, Armando Maestro, He Dong, Marité Cárdenas and Reidar Lund. RSC Adv., 2020,10, 35329-35340. DOI: 10.1039/D0RA07679A. The article is included in the thesis. Also available at: https://doi.org/10.1039/D0RA07679A |