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Microscopic agents programmed by DNA circuits

Nature Nanotechnology volume 12, pages 351–359 (2017)Cite this article

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Abstract

Information stored in synthetic nucleic acids sequences can be used in vitro to create complex reaction networks with precisely programmed chemical dynamics. Here, we scale up this approach to program networks of microscopic particles (agents) dispersed in an enzymatic solution. Agents may possess multiple stable states, thus maintaining a memory and communicate by emitting various orthogonal chemical signals, while also sensing the behaviour of neighbouring agents. Using this approach, we can produce collective behaviours involving thousands of agents, for example retrieving information over long distances or creating spatial patterns. Our systems recapitulate some fundamental mechanisms of distributed decision making and morphogenesis among living organisms and could find applications in cases where many individual clues need to be combined to reach a decision, for example in molecular diagnostics.

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Figure 1: Programming microscopic agents using DNA-encoded reaction rules.
Figure 2: Positive feedback loop-encoded agents.
Figure 3: Travelling front propagation across a population of bistable agents (PαB).
Figure 4: ‘Go-fetch’ program using four agent populations.
Figure 5: Mixed populations of symbiotic particles.
Figure 6: Cooperative mechanism in symbiotic clusters.

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Acknowledgements

This work was supported by the JSPS with a Grant-in-Aid from the JSPS for Scientific Research on Innovative Areas ‘Synthetic Biology for Comprehension of Biomolecular Networks’ (no. 23119001) and an ERC Consolidator grant ‘ProFF’ (no. 647275). G.G. acknowledges financial support from the JSPS Postdoc program and the University Paris Sciences et Lettres. The authors thank N. Bredeche, N. Aubert-Kato and A. Genot for advice and Y. Tauran and A. Baccouche for expressing and purifying the exonuclease.

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Authors and Affiliations

  1. LIMMS, CNRS, Institute of Industrial Science, University of Tokyo, Tokyo, 153–8505, Japan

    G. Gines, T. Fujii & Y. Rondelez

  2. Laboratoire Gulliver, CNRS, ESPCI Paris, PSL Research University, 10 rue Vauquelin, Paris, 75005, France

    G. Gines, A. S. Zadorin & Y. Rondelez

  3. Laboratoire Jean Perrin, CNRS, Université Pierre et Marie Curie, UMR 8237, 4 place Jussieu, Paris, 75005, France

    A. S. Zadorin, J.-C. Galas & A. Estevez-Torres

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Contributions

G.G. designed the study, performed experiments, analysed the data and wrote the manuscript. A.S.Z. carried out mathematical analysis, contributed to image analysis and manuscript writing. J.-C.G. and A.E.-T. contributed to the experimental set-up and designed the study. T.F. provided support with the microfluidic platform. Y.R. conceived, designed and supervised the study, analysed the data and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Y. Rondelez.

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Competing interests

G.G., Y.R. and T.F. have submitted a patent application related to the results presented in this paper.

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Gines, G., Zadorin, A., Galas, JC. et al. Microscopic agents programmed by DNA circuits. Nature Nanotech 12, 351–359 (2017). https://doi.org/10.1038/nnano.2016.299

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