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Current understanding of biological identity at the nanoscale and future prospects

Abstract

Nanoscale objects are processed by living organisms using highly evolved and sophisticated endogenous cellular networks, specifically designed to manage objects of this size. While these processes potentially allow nanostructures unique access to and control over key biological machineries, they are also highly protected by cell or host defence mechanisms at all levels. A thorough understanding of bionanoscale recognition events, including the molecules involved in the cell recognition machinery, the nature of information transferred during recognition processes and the coupled downstream cellular processing, would allow us to achieve a qualitatively novel form of biological control and advanced therapeutics. Here we discuss evolving fundamental microscopic and mechanistic understanding of biological nanoscale recognition. We consider the interface between a nanostructure and a target cell membrane, outlining the categories of nanostructure properties that are recognized, and the associated nanoscale signal transduction and cellular programming mechanisms that constitute biological recognition.

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Fig. 1: Formation of the bionanoscale synapse.
Fig. 2: The hard and soft biomolecular corona paradigm in nanoscale recognition.
Fig. 3: Nanoscale mapping determines the composition and spatial distribution of recognition motifs on a particle-by-particle basis.
Fig. 4: Recognition from the cell perspective.

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Acknowledgements

K.A.D. and Y.Y. acknowledge that this publication has emanated from research supported in part by a grant from Science Foundation Ireland (17/NSFC/4898 (K.A.D.)), funding under Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment (2019KSYS008 (K.A.D.)) and grants from Science Foundation Ireland (15/SIRG/3423 (Y.Y.), 17/ERCD/4962 (K.A.D.) and 16/ENM-ERA/3457 (Y.Y.)). We would like to thank Yijun Jiang, Guangzhou Hongjun Scientific Co., Ltd, for creating the images in Figs. 1, 2, 3a,e,g,i,k and 4.

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Correspondence to Kenneth A. Dawson or Yan Yan.

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Peer review information Nature Nanotechnology thanks Jie Zheng and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Video 1

Live-cell imaging of nanoparticle–cell interactions. Cells in the exponential growth phase were seeded in a confocal dish 24 h before the imaging. After the cell membrane was stained with CellMask Orange, the cells were treated with fluorescein isothiocyanate-labelled polystyrene nanoparticles (100 nm in diameter). Subsequently, the cells were placed in a live-cell imaging chamber and imaged using spinning disc microscopy with a ×63 lens (oil immersion).

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Dawson, K.A., Yan, Y. Current understanding of biological identity at the nanoscale and future prospects. Nat. Nanotechnol. (2021). https://doi.org/10.1038/s41565-021-00860-0

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