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A stochastic DNA walker that traverses a microparticle surface

Abstract

Molecular machines have previously been designed that are propelled by DNAzymes1,2,3, protein enzymes4,5,6 and strand displacement7,8,9. These engineered machines typically move along precisely defined one- and two-dimensional tracks. Here, we report a DNA walker that uses hybridization to drive walking on DNA-coated microparticle surfaces. Through purely DNA:DNA hybridization reactions, the nanoscale movements of the walker can lead to the generation of a single-stranded product and the subsequent immobilization of fluorescent labels on the microparticle surface. This suggests that the system could be of use in analytical and diagnostic applications, similar to how strand exchange reactions in solution have been used for transducing and quantifying signals from isothermal molecular amplification assays10,11. The walking behaviour is robust and the walker can take more than 30 continuous steps. The traversal of an unprogrammed, inhomogeneous surface is also due entirely to autonomous decisions made by the walker, behaviour analogous to amorphous chemical reaction network computations12,13, which have been shown to lead to pattern formation14,15,16,17.

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Figure 1: Schematic and proof-of-concept for CHA on microparticles.
Figure 2: Double catalyst walking behaviour detected with flow cytometry.
Figure 3: Interpretation of walking behaviour with numerical simulation.
Figure 4: Fluorescence microscopy of CHA on microparticles.
Figure 5: Amplification of miRNA detection using a walker.

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References

  1. 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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Bath, J., Green, S. J. & Turberfield, A. J. A free-running DNA motor powered by a nicking enzyme. Angew. Chem. Int. Ed. 117, 4432–4435 (2005).

    Article  Google Scholar 

  5. Wickham, S. F. J. et al. Direct observation of stepwise movement of a synthetic molecular transporter. Nature Nanotech. 6, 166–169 (2011).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Green, S., Bath, J. & Turberfield, A. Coordinated chemomechanical cycles: a mechanism for autonomous molecular motion. Phys. Rev. Lett. 101, 238101 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Li, B., Chen, X. & Ellington, A. D. Adapting enzyme-free DNA circuits to the detection of loop-mediated isothermal amplification reactions. Anal. Chem. 84, 8371–8377 (2012).

    Article  CAS  Google Scholar 

  11. Jiang, Y. S., Li, B., Milligan, J. N., Bhadra, S. & Ellington, A. D. Real-time detection of isothermal amplification reactions with thermostable catalytic hairpin assembly. J. Am. Chem. Soc. 135, 7430–7433 (2013).

    Article  CAS  Google Scholar 

  12. 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 

  13. Chen, Y.-J. et al. Programmable chemical controllers made from DNA. Nature Nanotech. 8, 755–762 (2013).

    Article  CAS  Google Scholar 

  14. Isalan, M., Lemerle, C. & Serrano, L. Engineering gene networks to emulate Drosophila embryonic pattern formation. PLoS Biol. 3, e64 (2005).

    Article  Google Scholar 

  15. Simpson, Z. B., Tsai, T. L., Nguyen, N., Chen, X. & Ellington, A. D. Modelling amorphous computations with transcription networks. J. R. Soc. Interface 6, S523–S533 (2009).

    Article  CAS  Google Scholar 

  16. Padirac, A., Fujii, T., Estévez-Torres, A. & Rondelez, Y. Spatial waves in synthetic biochemical networks. J. Am. Chem. Soc. 135, 14586–14592 (2013).

    Article  CAS  Google Scholar 

  17. Chirieleison, S. M., Allen, P. B., Simpson, Z. B., Ellington, A. D. & Chen, X. Pattern transformation with DNA circuits. Nature Chem. 5, 1000–1005 (2013).

    Article  CAS  Google Scholar 

  18. 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).

  19. Wang, Z.-G., Elbaz, J. & Willner, I. DNA machines: bipedal walker and stepper. Nano Lett. 11, 304–309 (2011).

    Article  CAS  Google Scholar 

  20. Goldstein, B. et al. Competition between solution and cell surface receptors for ligand. Dissociation of hapten bound to surface antibody in the presence of solution antibody. Biophys. J. 56, 955–966 (1989).

    Article  CAS  Google Scholar 

  21. Walsh, M. K., Wang, X. & Weimer, B. C. Optimizing the immobilization of single-stranded DNA onto glass beads. J. Biochem. Biophys. Methods 47, 221–231 (2001).

    Article  CAS  Google Scholar 

  22. Dunbar, S. A. Applications of Luminex® xMAPTM technology for rapid, high-throughput multiplexed nucleic acid detection. Clin. Chim. Acta 363, 71–82 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Wu, Y., Zhang, D. Y., Yin, P. & Vollmer, F. Ultraspecific and highly sensitive nucleic acid detection by integrating a DNA catalytic network with a label-free microcavity. Small 10, 2067–2076 (2014).

    Article  CAS  Google Scholar 

  26. Yang, B. et al. Intelligent layered nanoflare: ‘lab-on-a-nanoparticle’ for multiple DNA logic gate operations and efficient intracellular delivery. Nanoscale 6, 8990–8996 (2014).

    Article  CAS  Google Scholar 

  27. Fernandez, J. G. & Khademhosseini, A. Micro-masonry: construction of 3D structures by microscale self-assembly. Adv. Mater. 22, 2538–2541 (2010).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was funded by the National Institutes of Health (EUREKA, 1-R01-GM094933), The Welch Foundation (F-1654) and a National Security Science and Engineering Faculty Fellowship (FA9550-10-1-0169). The authors also acknowledge D. Stefanovic for his helpful discussion of the modelling system.

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Authors and Affiliations

Authors

Contributions

C.J. and P.B.A. conceived the walker scheme. C.J. performed most of the experiments. P.B.A. carried out a fluorescence microscopy experiment and performed modelling and analysis. A.D.E. supervised the project. C.J., P.B.A. and A.D.E. wrote the manuscript.

Corresponding author

Correspondence to A. D. Ellington.

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The authors declare no competing financial interests.

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Jung, C., Allen, P. & Ellington, A. A stochastic DNA walker that traverses a microparticle surface. Nature Nanotech 11, 157–163 (2016). https://doi.org/10.1038/nnano.2015.246

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