journal article·2021-06-22Open access

Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation

Katharine Hammond, Flaviu Cipcigan, Kareem Al Nahas, Valeria Losasso, Helen Lewis, Jehangir Cama, Fausto Martelli, Patrick W. Simcock, Marcus Fletcher, Jascindra Ravi, Phillip J. Stansfeld, Stefano Pagliara, Bart W. Hoogenboom, Ulrich F. Keyser, Mark S. P. Sansom, Jason Crain, Maxim G. Ryadnov

ACS Nano· Volume 15· Issue 6

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Antimicrobial Peptides and Activities · Lipid Membrane Structure and Behavior · Nanopore and Nanochannel Transport Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

National Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.

London Centre for Nanotechnology, University College London, London WC1H 0AH, U.K.

IBM Research Europe, Hartree Centre, Daresbury WA4 4AD, U.K.

Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, U.K.

STFC Daresbury Laboratories, Daresbury WA4 4AD, U.K.

Living Systems Institute, University of Exeter, Exeter EX4 4QD, U.K.

College of Engineering, Mathematics and Phys Sciences, University of Exeter, Exeter EX4 4QF, U.K.

Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.

College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, U.K.

Department of Physics & Astronomy, University College London, London WC1E 6BT, U.K.

Department of Physics, King’s College London, London, WC2R 2LS, U.K.

Funding

Engineering and Physical Sciences Research Council · Royal Society · Medical Research Council · Department for Business, Energy and Industrial Strategy, UK Government · University of Cambridge · Wellcome Trust · H2020 European Research Council

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