Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

High-speed DNA-based rolling motors powered by RNase H

Nature Nanotechnology volume 11, pages 184–190 (2016)Cite this article

Subjects

This article has been updated

Abstract

DNA-based machines that walk by converting chemical energy into controlled motion could be of use in applications such as next-generation sensors, drug-delivery platforms and biological computing. Despite their exquisite programmability, DNA-based walkers are challenging to work with because of their low fidelity and slow rates (∼1 nm min–1). Here we report DNA-based machines that roll rather than walk, and consequently have a maximum speed and processivity that is three orders of magnitude greater than the maximum for conventional DNA motors. The motors are made from DNA-coated spherical particles that hybridize to a surface modified with complementary RNA; the motion is achieved through the addition of RNase H, which selectively hydrolyses the hybridized RNA. The spherical motors can move in a self-avoiding manner, and anisotropic particles, such as dimerized or rod-shaped particles, can travel linearly without a track or external force. We also show that the motors can be used to detect single nucleotide polymorphism by measuring particle displacement using a smartphone camera.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Approach used to generate RNA-fuelled, enzyme-catalysed autonomous DNA motors.
Figure 2: Characterization of particle motion driven by RNase H.
Figure 3: Elucidating the mechanism of particle motion and determining factors that influence particle velocity.
Figure 4: Directional motor translocation from self-avoiding to ballistic.
Figure 5: SNP detection with a smartphone microscope.

Similar content being viewed by others

Change history

  • 10 December 2015

    In this Article, the wrong version of Fig. 1a was used. This error has now been corrected in all versions of the Article.

References

  1. He, Y. & Liu, D. R. Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker. Nature Nanotech. 5, 778–782 (2010).

    Article  CAS  Google Scholar 

  2. Lewandowski, B. et al. Sequence-specific peptide synthesis by an artificial small-molecule machine. Science 339, 189–193 (2013).

    Article  CAS  Google Scholar 

  3. von Delius, M., Geertsema, E. M. & Leigh, D. A. A synthetic small molecule that can walk down a track. Nature Chem. 2, 96–101 (2010).

    Article  CAS  Google Scholar 

  4. Paxton, W. F., Sundararajan, S., Mallouk, T. E. & Sen, A. Chemical locomotion. Angew. Chem. Int. Ed. 45, 5420–5429 (2006).

    Article  CAS  Google Scholar 

  5. Pavlick, R. A., Sengupta, S., McFadden, T., Zhang, H. & Sen, A. A polymerization-powered motor. Angew. Chem. Int. Ed. 50, 9374–9377 (2011).

    Article  CAS  Google Scholar 

  6. Orozco, J. et al. Artificial enzyme-powered microfish for water-quality testing. ACS Nano 7, 818–824 (2013).

    Article  CAS  Google Scholar 

  7. 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 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. 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 

  13. Yin, P., Choi, H. M. T., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–U314 (2008).

    Article  CAS  Google Scholar 

  14. 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 

  15. 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 

  16. Perl, A. et al. Gradient-driven motion of multivalent ligand molecules along a surface functionalized with multiple receptors. Nature Chem. 3, 317–322 (2011).

    Article  CAS  Google Scholar 

  17. Fang, S., Lee, H. J., Wark, A. W., Kim, H. M. & Corn, R. M. Determination of ribonuclease H surface enzyme kinetics by surface plasmon resonance imaging and surface plasmon fluorescence spectroscopy. Anal. Chem. 77, 6528–6534 (2005).

    Article  CAS  Google Scholar 

  18. Yehl, K. et al. Catalytic deoxyribozyme-modified nanoparticles for RNAi-independent gene regulation. ACS Nano 6, 9150–9157 (2012).

    Article  CAS  Google Scholar 

  19. Liu, Y., Yehl, K., Narui, Y. & Salaita, K. Tension sensing nanoparticles for mechano-imaging at the living/nonliving interface. J. Am. Chem. Soc. 135, 5320–5323 (2013).

    Article  CAS  Google Scholar 

  20. Liu, Y. et al. Nanoparticle tension probes patterned at the nanoscale: impact of integrin clustering on force transmission. Nano Lett. 14, 5539–5546 (2014).

    Article  CAS  Google Scholar 

  21. Sbalzarini, I. F. & Koumoutsakos, P. Feature point tracking and trajectory analysis for video imaging in cell biology. J. Struct. Biol. 151, 182–195 (2005).

    Article  CAS  Google Scholar 

  22. Gal, N., Lechtman-Goldstein, D. & Weihs, D. Particle tracking in living cells: a review of the mean square displacement method and beyond. Rheol. Acta 52, 425–443 (2013).

    Article  CAS  Google Scholar 

  23. Domb, C., Gillis, J. & Wilmers, G. On shape and configuration of polymer molecules. Proc. Phys. Soc. 85, 625 (1965).

    Article  CAS  Google Scholar 

  24. Amit, D. J., Parisi, G. & Peliti, L. Asymptotic-behavior of the true self-avoiding walk. Phys. Rev. B 27, 1635–1645 (1983).

    Article  Google Scholar 

  25. Obukhov, S. P. & Peliti, L. Renormalization of the true self-avoiding walk. J. Phys. A 16, L147–L151 (1983).

    Article  Google Scholar 

  26. Family, F. & Daoud, M. Experimental realization of true self-avoiding walks. Phys. Rev. B 29, 1506–1507 (1984).

    Article  CAS  Google Scholar 

  27. Diehl, M. R., Zhang, K., Lee, H. J. & Tirrell, D. A. Engineering cooperativity in biomotor–protein assemblies. Science 311, 1468–1471 (2006).

    Article  CAS  Google Scholar 

  28. Østergaard, M. E. et al. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res. 41, 9634–9650 (2013).

    Article  Google Scholar 

  29. Berna, J. et al. Macroscopic transport by synthetic molecular machines. Nature Mater. 4, 704–710 (2005).

    Article  CAS  Google Scholar 

  30. Eelkema, R. et al. Nanomotor rotates microscale objects. Nature 440, 163–163 (2006).

    Article  CAS  Google Scholar 

  31. Liu, Y. et al. Linear artificial molecular muscles. J. Am. Chem. Soc. 127, 9745–9759 (2005).

    Article  CAS  Google Scholar 

  32. Wang, W., Chiang, T. Y., Velegol, D. & Mallouk, T. E. Understanding the efficiency of autonomous nano- and microscale motors. J. Am. Chem. Soc. 135, 10557–10565 (2013).

    Article  CAS  Google Scholar 

  33. Peterson, A. W., Heaton, R. J. & Georgiadis, R. M. The effect of surface probe density on DNA hybridization. Nucleic Acids Res. 29, 5163–5168 (2001).

    Article  CAS  Google Scholar 

  34. Yan, L., Zhao, X. M. & Whitesides, G. M. Patterning a preformed, reactive SAM using microcontact printing. J. Am. Chem. Soc. 120, 6179–6180 (1998).

    Article  CAS  Google Scholar 

  35. Zhang, Y., Ge, C. H., Zhu, C. & Salaita, K. DNA-based digital tension probes reveal integrin forces during early cell adhesion. Nature Commun. 5, 5167 (2014).

    Article  CAS  Google Scholar 

  36. Johnson, K. A. & Goody, R. S. The original Michaelis constant: translation of the 1913 Michaelis–Menten paper. Biochemistry 50, 8264–8269 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

K.S. is grateful for support from the National Institutes of Health through R01-GM097399, the Alfred P. Sloan Research Fellowship, the Camille–Dreyfus Teacher–Scholar Award and the National Science Foundation (NSF) CAREER Award (1350829). K.Y. thanks the ARCS Foundation for their support and V. Pui-Yan Ma for generating Fig. 1. We also thank S. Urazhdin for access to the thermal evaporator and M. Grover and D. Stabley for helpful discussions. E.R.W. was funded by the NSF (CMMI-1250235) and S.V. was funded by Emory University. This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core.

Author information

Authors and Affiliations

  1. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, 30322, Georgia, USA

    Kevin Yehl, Yang Liu, Yun Zhang, Mengzhen Fan & Khalid Salaita

  2. Department of Physics, Emory University, 400 Dowman Drive, Atlanta, 30322, Georgia, USA

    Andrew Mugler, Skanda Vivek & Eric R. Weeks

  3. Department of Physics, Purdue University, West Lafayette, 47907, Indiana, USA

    Andrew Mugler

Authors
  1. Kevin Yehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew Mugler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Skanda Vivek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mengzhen Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eric R. Weeks
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Khalid Salaita
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.Y. conducted all the experiments and analysis, A.M. performed the simulations and theoretical validation, S.V. helped in the data analysis and validation of the theoretical model, Y.Z. helped with particle functionalization, Y.L. collected SIM data, M.F. assisted with SNP detection, K.S. and K.Y. wrote the manuscript with input from A.M. and E.R.W., K.S. oversaw all the aspects of the work and E.R.W. supervised and discussed the experiments with S.V.

Corresponding author

Correspondence to Khalid Salaita.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Information (PDF 3610 kb)

Supplementary Movie 1

Supplementary Movie 1 (AVI 2675 kb)

Supplementary Movie 2

Supplementary Movie 2 (AVI 339 kb)

Supplementary Movie 3

Supplementary Movie 3 (AVI 250 kb)

Supplementary Movie 4

Supplementary Movie 4 (MP4 983 kb)

Supplementary Movie 5

Supplementary Movie 5 (AVI 2455 kb)

Supplementary Movie 6

Supplementary Movie 6 (AVI 310 kb)

Supplementary Movie 7

Supplementary Movie 7 (AVI 2476 kb)

Supplementary Movie 8

Supplementary Movie 8 (AVI 4785 kb)

Supplementary Movie 9

Supplementary Movie 9 (AVI 380 kb)

Supplementary Movie 10

Supplementary Movie 10 (AVI 2668 kb)

Supplementary Movie 11

Supplementary Movie 11 (AVI 4767 kb)

Supplementary Movie 12

Supplementary Movie 12 (AVI 233 kb)

Supplementary Movie 13

Supplementary Movie 13 (AVI 260 kb)

Supplementary Movie 14

Supplementary Movie 14 (AVI 0 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yehl, K., Mugler, A., Vivek, S. et al. High-speed DNA-based rolling motors powered by RNase H. Nature Nanotech 11, 184–190 (2016). https://doi.org/10.1038/nnano.2015.259

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2015.259

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing