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Molecular robots guided by prescriptive landscapes

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.

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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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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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