Hammond, K;
Cipcigan, F;
Al Nahas, K;
Losasso, V;
Lewis, H;
Cama, J;
Martelli, F;
... Ryadnov, MG; + view all
(2021)
Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation.
ACS Nano
, 15
(6)
pp. 9679-9689.
10.1021/acsnano.1c00218.
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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.
| Type: | Article |
|---|---|
| Title: | Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acsnano.1c00218 |
| Publisher version: | https://doi.org/10.1021/acsnano.1c00218 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission |
| Keywords: | antibiotics, de novo protein design, innate host defense, nanopores, nanoscale imaging |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10127676 |
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