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Reaction-diffusion patterning of DNA-based artificial cells

Adrian Leathers, Michal Walczak, Ryan A. Brady, Assala Al Samad, Jurij Kotar, Michael J. Booth, Pietro Cicuta, Lorenzo Di Michele
doi: https://doi.org/10.1101/2022.03.24.485404
Adrian Leathers
†Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
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Michal Walczak
†Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
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Ryan A. Brady
‡Department of Chemistry, Faculty of Natural and Mathematical Sciences, King’s College London, London SE1 1DB, UK
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Assala Al Samad
¶Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK
§Department of Chemistry, University College London, London WC1H 0AJ, UK
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Jurij Kotar
†Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
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Michael J. Booth
¶Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK
§Department of Chemistry, University College London, London WC1H 0AJ, UK
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Pietro Cicuta
†Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
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Lorenzo Di Michele
⊥fabriCELL, Imperial College London, Molecular Sciences Research Hub, London W12 0BZ, UK
†Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
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  • For correspondence: l.di-michele@imperial.ac.uk
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Abstract

Biological cells display complex internal architectures, with distinct micro environments that establish the chemical heterogeneity needed to sustain cellular functions. The continued efforts to create advanced cell mimics – artificial cells – demands strategies to robustly engineer micro-compartmentalised architectures, where the molecular makeup of distinct regions is coupled with localised functionalities. Here, we introduce a platform for constructing membrane-less artificial cells from the self-assembly of synthetic DNA nanostructures, in which internal domains can be established thanks to a rationally designed reactiondiffusion process. The method, rationalised through numerical modelling, enables the formation of up to five distinct and addressable environments, in which functional moieties can be localised. As a proof-of-concept, we apply this platform to build artificial cells in which a prototypical nucleus synthesises fluorescent RNA aptamers, which then accumulate in a surrounding storage shell, thus demonstrating spatial segregation of functionalities reminiscent of that observed in biological cells.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* E-mail: l.di-michele{at}imperial.ac.uk

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 24, 2022.
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Reaction-diffusion patterning of DNA-based artificial cells
Adrian Leathers, Michal Walczak, Ryan A. Brady, Assala Al Samad, Jurij Kotar, Michael J. Booth, Pietro Cicuta, Lorenzo Di Michele
bioRxiv 2022.03.24.485404; doi: https://doi.org/10.1101/2022.03.24.485404
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Reaction-diffusion patterning of DNA-based artificial cells
Adrian Leathers, Michal Walczak, Ryan A. Brady, Assala Al Samad, Jurij Kotar, Michael J. Booth, Pietro Cicuta, Lorenzo Di Michele
bioRxiv 2022.03.24.485404; doi: https://doi.org/10.1101/2022.03.24.485404

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