Molecular devices with information-processing capabilities hold great promise for developing intelligent nanorobotics. Here we demonstrate a DNA navigator system that can perform single-molecule parallel depth-first search on a ten-vertex rooted tree defined on a two-dimensional DNA origami platform. Pathfinding by the DNA navigators exploits a localized strand exchange cascade, which is initiated at a unique trigger site on the origami with subsequent automatic progression along paths defined by DNA hairpins containing a universal traversal sequence. Each single-molecule navigator autonomously explores one of the possible paths through the tree. A specific solution path connecting a given pair of start and end vertices can then be easily extracted from the set of all paths taken by the navigators collectively. The solution path laid out on origami is illustrated with single-molecule imaging. Our approach points towards the realization of molecular materials with embedded computational functions operating at the single-molecule level.

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  1. 1.

    Kudernac, T. et al. Electrically driven directional motion of a four-wheeled molecule on a metal surface. Nature 479, 208–211 (2011).

  2. 2.

    Hagiya, M., Konagaya, A., Kobayashi, S., Saito, H. & Murata, S. Molecular robots with sensors and intelligence. Acc. Chem. Res. 47, 1681–1690 (2014).

  3. 3.

    Kassem, S. et al. Artificial molecular motors. Chem. Soc. Rev. 46, 2592–2621 (2017).

  4. 4.

    Yin, P., Yan, H., Daniell, X. G., Turberfield, A. J. & Reif, J. H. A unidirectional DNA walker that moves autonomously along a track. Angew. Chem. Int. Ed. 43, 4906–4911 (2004).

  5. 5.

    Shin, J.-S. & Pierce, N. A. A synthetic DNA walker for molecular transport. J. Am. Chem. Soc. 126, 10834–10835 (2004).

  6. 6.

    Tian, Y., He, Y., Chen, Y., Yin, P. & Mao, C. A DNAzyme that walks processively and autonomously along a one-dimensional track. Angew. Chem. Int. Ed. 44, 4355–4358 (2005).

  7. 7.

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

  8. 8.

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

  9. 9.

    Wickham, S. F. J. et al. A DNA-based molecular motor that can navigate a network of tracks. Nat. Nanotech. 7, 169–173 (2012).

  10. 10.

    Tomov, T. E. et al. Rational design of DNA motors: Fuel optimization through single-molecule fluorescence. J. Am. Chem. Soc. 135, 11935–11941 (2013).

  11. 11.

    Cha, T.-G. et al. A synthetic DNA motor that transports nanoparticles along carbon nanotubes. Nat. Nanotech. 9, 39–43 (2014).

  12. 12.

    Kopperger, E., Pirzer, T. & Simmel, F. C. Diffusive transport of molecular cargo tethered to a DNA origami platform. Nano. Lett. 15, 2693–2699 (2015).

  13. 13.

    Yang, Y. et al. Direct visualization of walking motions of photocontrolled nanomachine on the DNA nanostructure. Nano. Lett. 15, 6672–6676 (2015).

  14. 14.

    Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, eaan6558 (2017).

  15. 15.

    Fan, C. & Pei, H. DNA nanotechnology. Chin. J. Chem. 34, 251 (2016).

  16. 16.

    Zhou, C., Duan, X. & Liu, N. A plasmonic nanorod that walks on DNA origami. Nat. Commun. 6, 8102 (2015).

  17. 17.

    Zhu, D. et al. A surface-confined proton-driven DNA pump using a dynamic 3D DNA scaffold. Adv. Mater. 28, 6860–6865 (2016).

  18. 18.

    Adleman, L. M. Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994).

  19. 19.

    Elbaz, J. et al. DNA computing circuits using libraries of DNAzyme subunits. Nat. Nanotech. 5, 417–422 (2010).

  20. 20.

    Pei, R., Matamoros, E., Liu, M., Stefanovic, D. & Stojanovic, M. N. Training a molecular automaton to play a game. Nat. Nanotech. 5, 773–777 (2010).

  21. 21.

    Macdonald, J. et al. Medium scale integration of molecular logic gates in an automaton. Nano. Lett. 6, 2598–2603 (2006).

  22. 22.

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

  23. 23.

    Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

  24. 24.

    Han, D. et al. A cascade reaction network mimicking the basic functional steps of adaptive immune response. Nat. Chem. 7, 835–841 (2015).

  25. 25.

    Li, J., Green, A. A., Yan, H. & Fan, C. H. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nat. Chem. 9, 1056–1067 (2017).

  26. 26.

    Liu, H., Wang, J., Song, S., Fan, C. & Gothelf, K. V. A DNA-based system for selecting and displaying the combined result of two input variables. Nat. Commun. 6, 10089 (2015).

  27. 27.

    Boemo, M. A., Lucas, A. E., Turberfield, A. J. & Cardelli, L. The formal language and design principles of autonomous DNA walker circuits. ACS Synth. Biol. 5, 878–884 (2016).

  28. 28.

    Chatterjee, G., Dalchau, N., Muscat, R. A., Phillips, A. & Seelig, G. A spatially localized architecture for fast and modular DNA computing. Nat. Nanotech. 12, 920–927 (2017).

  29. 29.

    Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

  30. 30.

    Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).

  31. 31.

    Voigt, N. V. et al. Single-molecule chemical reactions on DNA origami. Nat. Nanotech. 5, 200–203 (2010).

  32. 32.

    Lin, C. et al. Submicrometre geometrically encoded fluorescent barcodes self-assembled fromDNA. Nat. Chem. 4, 832–839 (2012).

  33. 33.

    Kuzyk, A. et al. DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response. Nature 483, 311–314 (2012).

  34. 34.

    Knudsen, J. B. et al. Routing of individual polymers in designed patterns. Nat. Nanotech. 10, 892–898 (2015).

  35. 35.

    Timm, C. & Niemeyer, C. M. Assembly and purification of enzyme-functionalized DNA origami structures. Angew. Chem. Int. Ed. 54, 6745–6750 (2015).

  36. 36.

    Edwardson, T. G. W., Lau, K. L., Bousmail, D., Serpell, C. J. & Sleiman, H. F. Transfer of molecular recognition information from DNA nanostructures to gold nanoparticles. Nat. Chem. 8, 162–170 (2016).

  37. 37.

    Zhang, Y. et al. Transfer of two-dimensional oligonucleotide patterns onto stereocontrolled plasmonic nanostructures through DNA-origami-based nanoimprinting lithography. Angew. Chem. Int. Ed. 55, 8036–8040 (2016).

  38. 38.

    Zhang, Z., Yang, Y., Pincet, F., C. Llaguno, M. & Lin, C. Placing and shaping liposomes with reconfigurable DNA nanocages. Nat. Chem. 9, 653–659 (2017).

  39. 39.

    Rao, V. N. & Kumar, V. Parallel depth first search. Part I. implementation. Int. J. Parallel Prog. 16, 479–499 (1987).

  40. 40.

    Dirks, R. M. & Pierce, N. A. Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–15278 (2004).

  41. 41.

    Lakin, M. R., Youssef, S., Polo, F., Emmott, S. & Phillips, A. Visual DSD: a design and analysis tool for DNA strand displacement systems. Bioinformatics 27, 3211–3213 (2011).

  42. 42.

    Moore, C. & Mertens, S. The Nature of Computation (Oxford Univ. Press, Oxford, 2011).

  43. 43.

    Scheible, M. B., Pardatscher, G., Kuzyk, A. & Simmel, F. C. Single molecule characterization of DNA binding and strand displacement reactions on lithographic DNA origami microarrays. Nano. Lett. 14, 1627–1633 (2014).

  44. 44.

    Jungmann, R. et al. Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT. Nat. Methods 11, 313–318 (2014).

  45. 45.

    Ovesný, M., Křížek, P., Borkovec, J., Švindrych, Z. & Hagen, G. M. ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging. Bioinformatics 30, 2389–2390 (2014).

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We greatly appreciate financial support from the Ministry of Science and Technology of China (2016YFA0201200), National Science Foundation of China (21390414, 21473236, 21675167, 21505148, 21722310, 61771253), and the Chinese Academy of Sciences (QYZDJ-SSW-SLH031). We further acknowledge support by the Deutsche Forschungsgemeinschaft through SFB1032 Project A2 and by the Technical University Munich International Graduate School
of Science and Engineering.

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Author notes

  1. These authors contributed equally: Jie Chao, Jianbang Wang, Fei Wang and Xiangyuan Ouyang.


  1. Key Laboratory for Organic Electronics & Information Displays (KLOEID), Institute of Advanced Materials (IAM) and School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing, China

    • Jie Chao
    • , Lianhui Wang
    •  & Wei Huang
  2. Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China

    • Jie Chao
    • , Jianbang Wang
    • , Xiangyuan Ouyang
    • , Huajie Liu
    • , Jiye Shi
    • , Lihua Wang
    • , Jun Hu
    •  & Chunhai Fan
  3. School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    • Fei Wang
    • , Qian Li
    •  & Chunhai Fan
  4. Joint Research Center for Precision Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai Fengxian Central Hospital, Shanghai, China

    • Fei Wang
  5. Physics of Synthetic Biological Systems (E14), Physics Department, Technische Universität München, Garching, Germany

    • Enzo Kopperger
    •  & Friedrich C. Simmel
  6. School of Chemical Science and Engineering, Tongji Univeristy, Shanghai, China

    • Huajie Liu
  7. Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China

    • Lihua Wang


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C.F. directed the research. C.F., F.C.S., H.L. and J.C. conceived the project and designed the experiments. J.C., J.W., F.W., X.O. and E.K. designed the DNA sequences, constructed the navigator system and performed the single-molecule studies. F.W., Q.L. and J.S. carried out the theoretical simulation. J.C., J.W., F.W., E.K., H.L., Lihua W., J.H., Lianhui W., W.H. and F.C.S. analysed the data. All authors discussed the results and commented on the manuscript. C.F., F.C.S. and H.L. co-wrote the paper.

Competing Interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Huajie Liu or Friedrich C. Simmel or Chunhai Fan.

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