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Pattern transformation with DNA circuits

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Abstract

Readily programmable chemical networks are important tools as the scope of chemistry expands from individual molecules to larger molecular systems. Although many complex systems are constructed using conventional organic and inorganic chemistry, the programmability of biological molecules such as nucleic acids allows for precise, high-throughput and automated design, as well as simple, rapid and robust implementation. Here we show that systematic and quantitative control over the diffusivity and reactivity of DNA molecules yields highly programmable chemical reaction networks (CRNs) that execute at the macroscale. In particular, we designed and implemented non-enzymatic DNA circuits capable of performing pattern-transformation algorithms such as edge detection. We also showed that it is possible to fine-tune and multiplex such circuits. We believe these strategies will provide programmable platforms on which to prototype CRNs, discover bottom-up construction principles and generate patterns in materials.

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Figure 1: High-level description and molecular detail of an incoherent feed-forward loop that performs edge detection.
Figure 2: Execution of the incoherent feed-forward loop that performs edge detection.
Figure 3: High-level description and molecular detail of the ‘positive edge’ circuit.
Figure 4: Execution of the ‘positive edge’ and ‘edge splitter’ circuits.
Figure 5: Combinatorial multiplexing of two-channel pattern-transformation programs.

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References

  1. Belowich, M. E. & Stoddart, J. F. Dynamic imine chemistry. Chem. Soc. Rev. 41, 2003–2024 (2012).

    Article  CAS  Google Scholar 

  2. Rowan, S. J., Cantrill, S. J., Cousins, G. R., Sanders, J. K. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002).

    Article  Google Scholar 

  3. Burda, C., Chen, X., Narayanan, R. & El-Sayed, M. A. Chemistry and properties of nanocrystals of different shapes. Chem. Rev. 105, 1025–1102 (2005).

    Article  CAS  Google Scholar 

  4. Rycenga, M. et al. Controlling the synthesis and assembly of silver nanostructures for plasmonic applications. Chem. Rev. 111, 3669–3712 (2011).

    Article  CAS  Google Scholar 

  5. Xia, Y., Xiong, Y., Lim, B. & Skrabalak, S. E. Shape-controlled synthesis of metal nanocrystals: simple chemistry meets complex physics? Angew. Chem. Int. Ed. 48, 60–103 (2009).

    Article  CAS  Google Scholar 

  6. Epstein, I. R. & Showalter, K. Nonlinear chemical dynamics: oscillations, patterns, and chaos. J. Phys. Chem. 100, 13132–13147 (1996).

    Article  CAS  Google Scholar 

  7. Sakurai, T., Mihaliuk, E., Chirila, F. & Showalter, K. Design and control of wave propagation patterns in excitable media. Science 296, 2009–2012 (2002).

    Article  CAS  Google Scholar 

  8. Bansagi, T. Jr, Vanag, V. K. & Epstein, I. R. Tomography of reaction–diffusion microemulsions reveals three-dimensional Turing patterns. Science 331, 1309–1312 (2011).

    Article  CAS  Google Scholar 

  9. Zaikin, A. N. & Zhabotinsky, A. M. Concentration wave propagation in two-dimensional liquid-phase self-oscillating system. Nature 225, 535–537 (1970).

    Article  CAS  Google Scholar 

  10. Adamatzky, A. & De Lacy Costello, B. Experimental logical gates in a reaction–diffusion medium: the XOR gate and beyond. Phys. Rev. E. 66, 046112 (2002).

    Article  Google Scholar 

  11. Vanag, V. K., Yang, L., Dolnik, M., Zhabotinsky, A. M. & Epstein, I. R. Oscillatory cluster patterns in a homogeneous chemical system with global feedback. Nature 406, 389–391 (2000).

    Article  CAS  Google Scholar 

  12. Petrov, V., Ouyang, Q. & Swinney, H. L. Resonant pattern formation in a chemical system. Nature 388, 655–657 (1997).

    Article  CAS  Google Scholar 

  13. Grzybowski, B. A. Chemistry in Motion: Reaction–Diffusion Systems for Micro- and Nanotechnology (Wiley, 2009).

  14. Adamatzky, A. I. Universal computation in excitable media: the 2+ medium. Adv. Mater. Opt. Electron. 7, 263–272 (1997).

    Article  CAS  Google Scholar 

  15. Hjelmfelt, A., Weinberger, E. D. & Ross, J. Chemical implementation of neural networks and Turing machines. Proc. Natl Acad. Sci. USA 88, 10983–10987 (1991).

    Article  CAS  Google Scholar 

  16. Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Challenges and opportunities for structural DNA nanotechnology. Nature Nanotech. 6, 763–772 (2011).

    Article  CAS  Google Scholar 

  17. Ke, Y., Ong, L. L., Shih, W. M. & Yin, P. Three-dimensional structures self-assembled from DNA bricks. Science 338, 1177–1183 (2012).

    Article  CAS  Google Scholar 

  18. Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012).

    Article  CAS  Google Scholar 

  19. Omabegho, T., Sha, R. & Seeman, N. C. A bipedal DNA Brownian motor with coordinated legs. Science 324, 67–71 (2009).

    Article  CAS  Google Scholar 

  20. Lund, K. et al. Molecular robots guided by prescriptive landscapes. Nature 465, 206–210 (2010).

    Article  CAS  Google Scholar 

  21. Gu, H., Chao, J., Xiao, S-J. & Seeman, N. C. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

    Article  CAS  Google Scholar 

  22. Kim, J. & Winfree, E. Synthetic in vitro transcriptional oscillators. Mol. Syst. Biol. 7, 465 (2011).

    Article  Google Scholar 

  23. Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006).

    Article  Google Scholar 

  24. Padirac, A., Fujii, T. & Rondelez, Y. Bottom-up construction of in vitro switchable memories. Proc. Natl Acad. Sci. USA 109, E3212–3220 (2012).

    Article  CAS  Google Scholar 

  25. Fujii, T. & Rondelez, Y. Predator–prey molecular ecosystems. ACS Nano 7, 27–34 (2013).

    Article  CAS  Google Scholar 

  26. Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).

    Article  CAS  Google Scholar 

  27. Zhang, D. Y., Turberfield, A. J., Yurke, B. & Winfree, E. Engineering entropy-driven reactions and networks catalyzed by DNA. Science 318, 1121–1125 (2007).

    Article  CAS  Google Scholar 

  28. Yin, P., Choi, H. M., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

    Article  CAS  Google Scholar 

  29. Stojanovic, M. N. & Stefanovic, D. A deoxyribozyme-based molecular automaton. Nature Biotech. 21, 1069–1074 (2003).

    Article  CAS  Google Scholar 

  30. Soloveichik, D., Seelig, G. & Winfree, E. DNA as a universal substrate for chemical kinetics. Proc. Natl Acad. Sci. USA 107, 5393–5398 (2010).

    Article  CAS  Google Scholar 

  31. Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011).

    Article  CAS  Google Scholar 

  32. Qian, L., Winfree, E. & Bruck, J. Neural network computation with DNA strand displacement cascades. Nature 475, 368–372 (2011).

    Article  CAS  Google Scholar 

  33. Kuhnert, L., Agladze, K. I. & Krinsky, V. I. Image-processing using light-sensitive chemical waves. Nature 337, 244–247 (1989).

    Article  CAS  Google Scholar 

  34. Basu, S., Gerchman, Y., Collins, C. H., Arnold, F. H. & Weiss, R. A synthetic multicellular system for programmed pattern formation. Nature 434, 1130–1134 (2005).

    Article  CAS  Google Scholar 

  35. Tabor, J. J. et al. A synthetic genetic edge detection program. Cell 137, 1272–1281 (2009).

    Article  Google Scholar 

  36. Li, B., Ellington, A. D. & Chen, X. Rational, modular adaptation of enzyme-free DNA circuits to multiple detection methods. Nucleic Acids Res. 39, e110 (2011).

    Article  CAS  Google Scholar 

  37. Chen, X., Briggs, N., McLain, J. R. & Ellington, A. D. Stacking nonenzymatic circuits for high signal gain. Proc. Natl Acad. Sci. USA 110, 5386–5391 (2013).

    Article  CAS  Google Scholar 

  38. Wagner, N. & Ashkenasy, G. Systems chemistry: logic gates, arithmetic units, and network motifs in small networks. Chem. Eur. J. 15, 1765–1775 (2009).

    Article  CAS  Google Scholar 

  39. Nitschke, J. R. Systems chemistry: molecular networks come of age. Nature 462, 736–738 (2009).

    Article  CAS  Google Scholar 

  40. von Kiedrowski, G., Otto, S. & Herdewijn, P. Welcome home, systems chemists! J. Syst. Chem. 1, 1 (2010).

    Article  Google Scholar 

  41. Kondo, S. & Miura, T. Reaction–diffusion model as a framework for understanding biological pattern formation. Science 329, 1616–1620 (2010).

    Article  CAS  Google Scholar 

  42. Allen, P. B., Chen, X., Simpson, Z. B. & Ellington, A. D. Modeling scalable pattern generation in DNA reaction network. Proc. Int. Conf. Sim. Synth. Living Syst. 13, 441–448 (2012).

    Article  Google Scholar 

  43. Abelson, H. et al. Amorphous computing. Commun. ACM 43, 74–82 (2000).

    Article  Google Scholar 

  44. Sacca, B. & Niemeyer, C. M. Functionalization of DNA nanostructures with proteins. Chem. Soc. Rev. 40, 5910–5921 (2011).

    Article  CAS  Google Scholar 

  45. Zadeh, J. N., Wolfe, B. R. & Pierce, N. A. Nucleic acid sequence design via efficient ensemble defect optimization. J. Comput. Chem. 32, 439–452 (2011).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Institute of Health (NIH) (R01GM094933) and a National Security Science and Engineering Faculty Fellowship (FA9550-10-1-0169). P.B.A. was supported by an NIH National Research Service Award Fellowship (1 F32 GM095280). X.C. was partially supported by a postdoctoral trainee fellowship from the Cancer Prevention Research Institute of Texas. We thank S. N. Adai for assistance with editing.

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Contributions

S.M.C. designed sequences for several circuits and performed the majority of the experiments. Z.B.S. and P.B.A. performed computer simulations. A.D.E. supervised the project and designed diffusion-programming tests and some quantitative analyses. X.C. conceived the project, designed most circuits and performed pilot experiments. S.M.C., X.C., P.B.A. and A.D.E. wrote the manuscript.

Corresponding authors

Correspondence to Andrew D. Ellington or Xi Chen.

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The authors declare no competing financial interests.

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Chirieleison, S., Allen, P., Simpson, Z. et al. Pattern transformation with DNA circuits. Nature Chem 5, 1000–1005 (2013). https://doi.org/10.1038/nchem.1764

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