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Diverse and robust molecular algorithms using reprogrammable DNA self-assembly

Author

Listed:
  • Damien Woods

    (California Institute of Technology
    Inria
    Maynooth University)

  • David Doty

    (California Institute of Technology
    University of California)

  • Cameron Myhrvold

    (Harvard University
    Harvard University)

  • Joy Hui

    (California Institute of Technology
    Harvard University)

  • Felix Zhou

    (California Institute of Technology
    University of Oxford)

  • Peng Yin

    (Harvard University
    Harvard University)

  • Erik Winfree

    (California Institute of Technology)

Abstract

Molecular biology provides an inspiring proof-of-principle that chemical systems can store and process information to direct molecular activities such as the fabrication of complex structures from molecular components. To develop information-based chemistry as a technology for programming matter to function in ways not seen in biological systems, it is necessary to understand how molecular interactions can encode and execute algorithms. The self-assembly of relatively simple units into complex products1 is particularly well suited for such investigations. Theory that combines mathematical tiling and statistical–mechanical models of molecular crystallization has shown that algorithmic behaviour can be embedded within molecular self-assembly processes2,3, and this has been experimentally demonstrated using DNA nanotechnology4 with up to 22 tile types5–11. However, many information technologies exhibit a complexity threshold—such as the minimum transistor count needed for a general-purpose computer—beyond which the power of a reprogrammable system increases qualitatively, and it has been unclear whether the biophysics of DNA self-assembly allows that threshold to be exceeded. Here we report the design and experimental validation of a DNA tile set that contains 355 single-stranded tiles and can, through simple tile selection, be reprogrammed to implement a wide variety of 6-bit algorithms. We use this set to construct 21 circuits that execute algorithms including copying, sorting, recognizing palindromes and multiples of 3, random walking, obtaining an unbiased choice from a biased random source, electing a leader, simulating cellular automata, generating deterministic and randomized patterns, and counting to 63, with an overall per-tile error rate of less than 1 in 3,000. These findings suggest that molecular self-assembly could be a reliable algorithmic component within programmable chemical systems. The development of molecular machines that are reprogrammable—at a high level of abstraction and thus without requiring knowledge of the underlying physics—will establish a creative space in which molecular programmers can flourish.

Suggested Citation

  • Damien Woods & David Doty & Cameron Myhrvold & Joy Hui & Felix Zhou & Peng Yin & Erik Winfree, 2019. "Diverse and robust molecular algorithms using reprogrammable DNA self-assembly," Nature, Nature, vol. 567(7748), pages 366-372, March.
  • Handle: RePEc:nat:nature:v:567:y:2019:i:7748:d:10.1038_s41586-019-1014-9
    DOI: 10.1038/s41586-019-1014-9
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    Cited by:

    1. Michael D. Dore & Muhammad Ghufran Rafique & Tianxiao Peter Yang & Marlo Zorman & Casey M. Platnich & Pengfei Xu & Tuan Trinh & Felix J. Rizzuto & Gonzalo Cosa & Jianing Li & Alba Guarné & Hanadi F. S, 2024. "Heat-activated growth of metastable and length-defined DNA fibers expands traditional polymer assembly," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Yahong Chen & Chaoyong Yang & Zhi Zhu & Wei Sun, 2022. "Suppressing high-dimensional crystallographic defects for ultra-scaled DNA arrays," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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