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Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides

[Image: see text] We report a physicochemical investigation of the lipid transport properties of model lipid membranes in the presence of the antimicrobial peptide indolicidin through comparisons of experimental SANS/SAXS scattering techniques to fully atomistic molecular dynamics simulations. In ag...

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Autores principales: Carrer, Manuel, Nielsen, Josefine Eilsø, Cezar, Henrique Musseli, Lund, Reidar, Cascella, Michele, Soares, Thereza A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424232/
https://www.ncbi.nlm.nih.gov/pubmed/37523748
http://dx.doi.org/10.1021/acs.jpclett.3c01284
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author Carrer, Manuel
Nielsen, Josefine Eilsø
Cezar, Henrique Musseli
Lund, Reidar
Cascella, Michele
Soares, Thereza A.
author_facet Carrer, Manuel
Nielsen, Josefine Eilsø
Cezar, Henrique Musseli
Lund, Reidar
Cascella, Michele
Soares, Thereza A.
author_sort Carrer, Manuel
collection PubMed
description [Image: see text] We report a physicochemical investigation of the lipid transport properties of model lipid membranes in the presence of the antimicrobial peptide indolicidin through comparisons of experimental SANS/SAXS scattering techniques to fully atomistic molecular dynamics simulations. In agreement with the experiment, we show that upon peripheral binding of the peptides, even at low concentrations, lipid flip-flop dynamics is greatly accelerated. Computer modeling elucidates the interplay between structural changes and lipid dynamics induced by peptides and proposes a mechanism for the mode of action of antimicrobial peptides, assessing the major role of entropy for the catalysis of the flipping events. The mechanism introduced here is universal for all peptides with preferential peripheral binding to the membrane as it does not depend on the specific amino acid sequence.
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spelling pubmed-104242322023-08-15 Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides Carrer, Manuel Nielsen, Josefine Eilsø Cezar, Henrique Musseli Lund, Reidar Cascella, Michele Soares, Thereza A. J Phys Chem Lett [Image: see text] We report a physicochemical investigation of the lipid transport properties of model lipid membranes in the presence of the antimicrobial peptide indolicidin through comparisons of experimental SANS/SAXS scattering techniques to fully atomistic molecular dynamics simulations. In agreement with the experiment, we show that upon peripheral binding of the peptides, even at low concentrations, lipid flip-flop dynamics is greatly accelerated. Computer modeling elucidates the interplay between structural changes and lipid dynamics induced by peptides and proposes a mechanism for the mode of action of antimicrobial peptides, assessing the major role of entropy for the catalysis of the flipping events. The mechanism introduced here is universal for all peptides with preferential peripheral binding to the membrane as it does not depend on the specific amino acid sequence. American Chemical Society 2023-07-31 /pmc/articles/PMC10424232/ /pubmed/37523748 http://dx.doi.org/10.1021/acs.jpclett.3c01284 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Carrer, Manuel
Nielsen, Josefine Eilsø
Cezar, Henrique Musseli
Lund, Reidar
Cascella, Michele
Soares, Thereza A.
Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title_full Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title_fullStr Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title_full_unstemmed Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title_short Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides
title_sort accelerating lipid flip-flop at low concentrations: a general mechanism for membrane binding peptides
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424232/
https://www.ncbi.nlm.nih.gov/pubmed/37523748
http://dx.doi.org/10.1021/acs.jpclett.3c01284
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