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Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment

Research output: Contribution to journalArticlepeer-review

Michal Walczak, Ryan A. Brady, Leonardo Mancini, Claudia Contini, Roger Rubio-Sánchez, William T. Kaufhold, Pietro Cicuta, Lorenzo Di Michele

Original languageEnglish
Article number4743
JournalNature Communications
Volume12
Issue number1
DOIs
PublishedDec 2021

Bibliographical note

Funding Information: M.W. acknowledges support from the Engineering and Physical Sciences Research Council (EPSRC), and the Department of Physics at the University of Cambridge (the McLatchie Trust fund). L.D.M. acknowledges support from a Royal Society University Research Fellowship (UF160152) and from the European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme (ERC-STG No 851667 NANOCELL). L.M. and P.C. acknowledge funding from the EPSRC (EP/T002778). C.C. acknowledges support from the Wellcome Trust Institutional Strategic Supporting Fund for an ISSF Springboard Fellowship (RSRO_67869). R.R.-S. acknowledges support from the Mexican National Council for Science and Technology (CONACYT, Grant No. 472427), the EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC, Grant No. EP/L015978), and from the Cambridge Trust. The authors thank Nicola Pellicciotta and Luigi Feriani for providing the DDM Matlab script. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecular cue, exposing the ‘sticky’ core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria.

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