Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain MutationClick to copy article linkArticle link copied!
- Katharine HammondKatharine HammondNational Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.London Centre for Nanotechnology, University College London, London WC1H 0AH, U.K.More by Katharine Hammond
- Flaviu Cipcigan
- Kareem Al NahasKareem Al NahasCavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, U.K.More by Kareem Al Nahas
- Valeria Losasso
- Helen LewisHelen LewisNational Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.More by Helen Lewis
- Jehangir CamaJehangir CamaLiving 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.More by Jehangir Cama
- Fausto Martelli
- Patrick W. SimcockPatrick W. SimcockDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.More by Patrick W. Simcock
- Marcus FletcherMarcus FletcherCavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, U.K.More by Marcus Fletcher
- Jascindra RaviJascindra RaviNational Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.More by Jascindra Ravi
- Phillip J. StansfeldPhillip J. StansfeldDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.More by Phillip J. Stansfeld
- Stefano PagliaraStefano PagliaraLiving Systems Institute, University of Exeter, Exeter EX4 4QD, U.K.College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, U.K.More by Stefano Pagliara
- Bart W. HoogenboomBart W. HoogenboomLondon Centre for Nanotechnology, University College London, London WC1H 0AH, U.K.Department of Physics & Astronomy, University College London, London WC1E 6BT, U.K.More by Bart W. Hoogenboom
- Ulrich F. KeyserUlrich F. KeyserCavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, U.K.More by Ulrich F. Keyser
- Mark S. P. SansomMark S. P. SansomDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.More by Mark S. P. Sansom
- Jason CrainJason CrainIBM Research Europe, Hartree Centre, Daresbury WA4 4AD, U.K.Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.More by Jason Crain
- Maxim G. Ryadnov*Maxim G. Ryadnov*Tel: (+44) 20 89436078. Email: [email protected]National Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.Department of Physics, King’s College London, London, WC2R 2LS, U.K.More by Maxim G. Ryadnov
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.
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