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Molecular robots guided by prescriptive landscapes

Nature volume 465, pages 206–210 (2010)Cite this article

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Abstract

Traditional robots1 rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment2,3,4. A first step in this direction was the development of DNA walkers5, which have developed from being non-autonomous6,7 to being capable of directed but brief motion on one-dimensional tracks8,9,10,11. Here we demonstrate that previously developed random walkers12—so-called molecular spiders that comprise a streptavidin molecule as an inert ‘body’ and three deoxyribozymes as catalytic ‘legs’—show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape13. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as ‘start’, ‘follow’, ‘turn’ and ‘stop’. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour14,15; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour2,16,17.

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Figure 1: Deoxyribozyme-based molecular walker and origami prescriptive landscape.
Figure 2: Spider movement along three tracks and AFM images of the spider at the START, on the TRACK and at the STOP site.
Figure 3: AFM movie of spider movement.
Figure 4: Spiders imaged on origami tracks in real time using super-resolution total-internal-reflection fluorescence microscopy.

References

  1. Siegwart, R. & Nourbakhsh, I. R. Introduction to Autonomous Mobile Robots (MIT Press, 2004)

    Google Scholar 

  2. Turing, A. M. On computable numbers, with an application to the Entscheidungsproblem. Proc. London Math. Soc. 42, 230–265 (1936)

    MathSciNet  MATH  Google Scholar 

  3. Braitenberg, V. Vehicles: Experiments in Synthetic Psychology (MIT Press, 1984)

    Google Scholar 

  4. Brooks, R. A. Intelligence without representation. Artif. Intell. 47, 139–159 (1991)

    Article  Google Scholar 

  5. Bath, J. & Turberfield, A. J. DNA nanomachines. Nature Nanotechnol. 2, 275–284 (2007)

    Article  ADS  CAS  Google Scholar 

  6. Sherman, W. B. & Seeman, N. C. A precisely controlled DNA biped walking device. Nano Lett. 4, 1203–1207 (2004)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Bath, J., Green, S. J. & Turberfield, A. J. A free-running DNA motor powered by a nicking enzyme. Angew. Chem. Int. Ed. 44, 4358–4361 (2005)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  12. Pei, R. et al. Behavior of polycatalytic assemblies in a substrate-displaying matrix. J. Am. Chem. Soc. 128, 12693–12699 (2006)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  14. Bonabeau, E., Dorigo, M. & Theraulaz, G. Swarm Intelligence: From Natural to Artificial Systems (Oxford Univ. Press, 1999)

    MATH  Google Scholar 

  15. Rus, D., Butler, Z., Kotay, K. & Vona, M. Self-reconfiguring robots. Commun. ACM 45, 39–45 (2002)

    Article  Google Scholar 

  16. Von Neumann, J. Theory of Self-Reproducing Automata (ed. Burks, A. W.) (Univ. Illinois Press, 1966)

    Google Scholar 

  17. Bennett, C. H. The thermodynamics of computation—a review. Int. J. Theor. Phys. 21, 905–940 (1982)

    Article  CAS  Google Scholar 

  18. Santoro, S. W. & Joyce, G. F. A general purpose RNA-cleaving DNA enzyme. Proc. Natl Acad. Sci. USA 94, 4262–4266 (1997)

    Article  ADS  CAS  Google Scholar 

  19. Antal, T. & Krapivsky, P. L. Molecular spiders with memory. Phys. Rev. E 76, 021121 (2007)

    Article  ADS  Google Scholar 

  20. Saffarian, S., Collier, I. E., Marmer, B. L., Elson, E. L. & Goldberg, G. Interstitial collagenase is a Brownian ratchet driven by proteolysis of collagen. Science 306, 108–111 (2004)

    Article  ADS  CAS  Google Scholar 

  21. Ke, Y., Lindsay, S., Chang, Y., Liu, Y. & Yan, H. Self-assembled water-soluble nucleic acid probe tiles for label-free RNA hybridization assays. Science 319, 180–183 (2008)

    Article  ADS  CAS  Google Scholar 

  22. Yurke, B., Turberfield, A. J., Mills, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000)

    Article  ADS  CAS  Google Scholar 

  23. Li, J., Zheng, W., Kwon, A. H. & Lu, Y. In vitro selection and characterization of a highly efficient Zn(II)-dependent RNA-cleaving deoxyribozyme. Nucleic Acids Res. 28, 481–488 (2000)

    Article  CAS  Google Scholar 

  24. Walter, N. G., Huang, C.-Y., Manzo, A. J. & Sobhy, M. A. Do-it-yourself guide: how to use the modern single-molecule toolkit. Nature Methods 5, 475–489 (2008)

    Article  CAS  Google Scholar 

  25. Churchman, L. S., Ökten, Z., Rock, R. S., Dawson, J. F. & Spudich, J. A. Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time. Proc. Natl Acad. Sci. USA 102, 1419–1423 (2005)

    Article  ADS  CAS  Google Scholar 

  26. Yildiz, A. & Selvin, P. R. Fluorescence imaging with one nanometer accuracy: application to molecular motors. Acc. Chem. Res. 38, 574–582 (2005)

    Article  CAS  Google Scholar 

  27. Hess, H. Toward devices powered by biomolecular motors. Science 312, 860–861 (2006)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the US National Science Foundation (NSF) EMT and CBC grants (all authors); fellowships and grants from the Kinship Foundation (Searle), the Leukemia & Lymphoma Society, the Juvenile Diabetes Research Foundation and NSF ITR (M.N.S.); awards from the US Army Research Office, the NSF, the US Office of Naval Research, the US National Institutes of Health, the US Department of Energy and a Sloan Research Fellowship (H.Y.); an NSF Graduate Fellowship (N.D.); and Molecular Biophysics and Microfluidics in Biomedical Sciences Training Fellowships from the NIH (A.J.-B. and N.M., respectively). M.N.S. is grateful to T. E. Mitchell and M. Olah for inspiration, discussions and help.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA,

    Kyle Lund, Jeanette Nangreave & Hao Yan

  2. The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA ,

    Kyle Lund, Jeanette Nangreave & Hao Yan

  3. Department of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, Michigan 48109, USA,

    Anthony J. Manzo, Nicole Michelotti, Alexander Johnson-Buck & Nils G. Walter

  4. Computation & Neural Systems, California Institute of Technology, Pasadena, California 91125, USA ,

    Nadine Dabby & Erik Winfree

  5. Department of Physics, University of Michigan, Ann Arbor, Michigan 48109, USA,

    Nicole Michelotti

  6. Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA,

    Steven Taylor, Renjun Pei & Milan N. Stojanovic

  7. Department of Biomedical Engineering, Columbia University, New York, New York 10032, USA,

    Milan N. Stojanovic

  8. Computer Science, California Institute of Technology, Pasadena, California 91125, USA ,

    Erik Winfree

  9. Bioengineering, California Institute of Technology, Pasadena, California 91125, USA ,

    Erik Winfree

Authors
  1. Kyle Lund
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Contributions

AFM experiments were performed by K.L. (majority), J.N. and N.D.; analysis was performed by N.D., K.L., J.N. and S.T. and supervised by E.W. and H.Y. Fluorescence microscopy and particle tracking analysis were performed by A.J.M., N.M. and A.J.-B, supervised by N.G.W. Spiders were synthesized and purified, and their integrity was confirmed and monitored, by S.T. Surface plasmon resonance experiments were performed by R.P. Research coordination was by M.N.S. and materials transfer coordination was by S.T., J.N. and K.L. Experimental design and manuscript preparation received input from all authors.

Corresponding authors

Correspondence to Milan N. Stojanovic, Nils G. Walter, Erik Winfree or Hao Yan.

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The authors declare no competing financial interests.

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This file contains a Supplementary Discussion, Supplementary Materials and Methods, Supplementary Figures 1-32 with legends, Supplementary Tables 1-4 and References. (PDF 8938 kb)

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Lund, K., Manzo, A., Dabby, N. et al. Molecular robots guided by prescriptive landscapes. Nature 465, 206–210 (2010). https://doi.org/10.1038/nature09012

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