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Switching cytolytic nanopores into antimicrobial fractal ruptures by a single side chain mutation
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Hammond, Katharine, Cipcigan, Flaviu, Al Nahas, Kareem, Losasso, Valeria, Lewis, Helen, Cama, Jehangir, Martelli, Fausto, Simcock, Patrick W., Fletcher, Marcus, Ravi, Jascindra, Stansfeld, Phillip J., Pagliara, Stefano, Hoogenboom, Bart W., Keyser, Ulrich F., Sansom, Mark S. P., Crain, Jason and Ryadnov, Maxim G. (2021) Switching cytolytic nanopores into antimicrobial fractal ruptures by a single side chain mutation. ACS Nano, 15 (6). pp. 9679-9689. doi:10.1021/acsnano.1c00218
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WRAP-Switching-cytolytic-nanopores-antimicrobial-fractal-ruptures-single-side-chain-mutation-2021.pdf - Accepted Version - Requires a PDF viewer. Download (2154Kb) | Preview |
Official URL: http://dx.doi.org/10.1021/acsnano.1c00218
Abstract
Disruption of cell membranes is a fundamental host defense response found in virtually all forms of life. The molecular mechanisms vary but generally lead to energetically favored circular nanopores. Here, we report an elaborate fractal rupture pattern induced by a single side-chain mutation in ultrashort (8–11-mers) helical peptides, which otherwise form transmembrane pores. In contrast to known mechanisms, this mode of membrane disruption is restricted to the upper leaflet of the bilayer where it exhibits propagating fronts of peptide-lipid interfaces that are strikingly similar to viscous instabilities in fluid flow. The two distinct disruption modes, pores and fractal patterns, are both strongly antimicrobial, but only the fractal rupture is nonhemolytic. The results offer wide implications for elucidating differential membrane targeting phenomena defined at the nanoscale.
| Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cell membranes , Antibiotics , Nanopores , Scanning probe microscopy, Bilayer lipid membranes | |||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | ACS Nano | |||||||||||||||||||||||||||||||||||||||
| Publisher: | American Chemical Society | |||||||||||||||||||||||||||||||||||||||
| ISSN: | 1936-0851 | |||||||||||||||||||||||||||||||||||||||
| Official Date: | 22 April 2021 | |||||||||||||||||||||||||||||||||||||||
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| Volume: | 15 | |||||||||||||||||||||||||||||||||||||||
| Number: | 6 | |||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 9679-9689 | |||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1021/acsnano.1c00218 | |||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||
| Reuse Statement (publisher, data, author rights): | “This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.html].” | |||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||||||||||||||
| Copyright Holders: | © 2021 American Chemical Society | |||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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