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.

Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns

Nature volume 552, pages 67–71 (2017)Cite this article

Subjects

Abstract

Self-assembled DNA nanostructures1 enable nanometre-precise patterning that can be used to create programmable molecular machines2,3,4,5,6 and arrays of functional materials7,8,9. DNA origami10 is particularly versatile in this context because each DNA strand in the origami nanostructure occupies a unique position and can serve as a uniquely addressable pixel. However, the scale of such structures11,12,13,14 has been limited to about 0.05 square micrometres, hindering applications that demand a larger layout15 and integration with more conventional patterning methods. Hierarchical multistage assembly of simple sets of tiles16,17 can in principle overcome this limitation, but so far has not been sufficiently robust to enable successful implementation of larger structures using DNA origami tiles. Here we show that by using simple local assembly rules18 that are modified and applied recursively throughout a hierarchical, multistage assembly process, a small and constant set of unique DNA strands can be used to create DNA origami arrays of increasing size and with arbitrary patterns. We illustrate this method, which we term ‘fractal assembly’, by producing DNA origami arrays with sizes of up to 0.5 square micrometres and with up to 8,704 pixels, allowing us to render images such as the Mona Lisa and a rooster. We find that self-assembly of the tiles into arrays is unaffected by changes in surface patterns on the tiles, and that the yield of the fractal assembly process corresponds to about 0.95m − 1 for arrays containing m tiles. When used in conjunction with a software tool that we developed that converts an arbitrary pattern into DNA sequences and experimental protocols, our assembly method is readily accessible and will facilitate the construction of sophisticated materials and devices with sizes similar to that of a bacterium using DNA nanostructures.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1: Design of fractal assembly.
Figure 2: Implementation with DNA origami tiles.
Figure 3: Automated design and experiments.

References

  1. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982)

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  3. 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  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  7. Maune, H. T. et al. Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates. Nat. Nanotechnol. 5, 61–66 (2010)

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  9. Gopinath, A., Miyazono, E., Faraon, A. & Rothemund, P. W. Engineering and mapping nanocavity emission via precision placement of DNA origami. Nature 535, 401–405 (2016)

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  11. Woo, S. & Rothemund, P. W. Programmable molecular recognition based on the geometry of DNA nanostructures. Nat. Chem. 3, 620–627 (2011)

    Article  CAS  Google Scholar 

  12. Rajendran, A., Endo, M., Katsuda, Y., Hidaka, K. & Sugiyama, H. Programmed two-dimensional self-assembly of multiple DNA origami jigsaw pieces. ACS Nano 5, 665–671 (2011)

    Article  CAS  Google Scholar 

  13. Zhao, Z., Liu, Y. & Yan, H. Organizing DNA origami tiles into larger structures using preformed scaffold frames. Nano Lett. 11, 2997–3002 (2011)

    Article  CAS  ADS  Google Scholar 

  14. Marchi, A. N., Saaem, I., Vogen, B. N., Brown, S. & LaBean, T. H. Toward larger DNA origami. Nano Lett. 14, 5740–5747 (2014)

    Article  CAS  ADS  Google Scholar 

  15. Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Challenges and opportunities for structural DNA nanotechnology. Nat. Nanotechnol. 6, 763–772 (2011)

    Article  CAS  ADS  Google Scholar 

  16. Doty, D. Theory of algorithmic self-assembly. Commun. ACM 55, 78–88 (2012)

    Article  Google Scholar 

  17. Park, S. H. et al. Finite-size, fully addressable DNA tile lattices formed by hierarchical assembly procedures. Angew. Chem. 118, 749–753 (2006)

    Article  Google Scholar 

  18. Tikhomirov, G., Petersen, P. & Qian, L. Programmable disorder in random DNA tilings. Nat. Nanotechnol. 12, 251–259 (2017)

    Article  CAS  ADS  Google Scholar 

  19. Mandelbrot, B. B. The Fractal Geometry of Nature (W. H. Freeman and Co., 1982)

  20. Nangreave, J., Yan, H. & Liu, Y. Studies of thermal stability of multivalent DNA hybridization in a nanostructured system. Biophys. J. 97, 563–571 (2009)

    Article  CAS  ADS  Google Scholar 

  21. Rinker, S., Ke, Y., Liu, Y., Chhabra, R. & Yan, H. Self-assembled DNA nanostructures for distance-dependent multivalent ligand–protein binding. Nat. Nanotechnol. 3, 418–422 (2008)

    Article  CAS  Google Scholar 

  22. Schreiber, R. et al. Hierarchical assembly of metal nanoparticles, quantum dots and organic dyes using DNA origami scaffolds. Nat. Nanotechnol. 9, 74–78 (2014)

    Article  CAS  ADS  Google Scholar 

  23. Castro, C. E. et al. A primer to scaffolded DNA origami. Nat. Methods 8, 221–229 (2011)

    Article  CAS  Google Scholar 

  24. Chemical synthesis and purification of oligonucleotideshttps://www.idtdna.com/pages/docs/technical-reports/chemical-synthesis-of-oligonucleotides.pdf (Integrated DNA Technologies, 2005)

  25. Petersen, P. FracTile Compilerhttp://qianlab.caltech.edu/FracTileCompiler (2017)

  26. Zenk, J., Tuntivate, C. & Schulman, R. Kinetics and thermodynamics of Watson–Crick base pairing driven DNA origami dimerization. J. Am. Chem. Soc. 138, 3346–3354 (2016)

    Article  CAS  Google Scholar 

  27. Lin, C., Perrault, S. D., Kwak, M., Graf, F. & Shih, W. M. Purification of DNA-origami nanostructures by rate-zonal centrifugation. Nucleic Acids Res. 41, e40 (2013)

    Article  CAS  Google Scholar 

  28. Xia, Y. & Whitesides, G. M. Soft lithography. Annu. Rev. Mater. Sci. 28, 153–184 (1998)

    Article  CAS  ADS  Google Scholar 

  29. Chandran, H., Gopalkrishnan, N., Phillips, A. & Reif, J. Localized hybridization circuits. Lect. Notes Comput. Sci. 6937, 64–83 (2011)

    Article  Google Scholar 

  30. Qian, L. & Winfree, E. Parallel and scalable computation and spatial dynamics with DNA-based chemical reaction networks on a surface. Lect. Notes Comput. Sci. 8727, 114–131 (2014)

    Article  Google Scholar 

  31. Delbrück, T. & Mead, C. in Vision Chips: Implementing Vision Algorithms with Analog VLSI Circuits (eds Koch, C. & Li, H. ) 139–161 (IEEE, 1995)

Download references

Acknowledgements

We thank R. M. Murray for sharing an acoustic liquid-handling robot and P. W. K. Rothemund for sharing a qPCR machine. We thank E. Winfree and P. W. K. Rothemund for critiques on the manuscript. G.T. was supported by a BWF grant (1010684). P.P. was supported by a NIH/NRSA training grant (5 T32 GM07616). L.Q. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (1010684) and a Faculty Early Career Development Award from NSF (1351081).

Author information

Author notes

  1. Grigory Tikhomirov and Philip Petersen: These authors contributed equally to this work.

Authors and Affiliations

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

    Grigory Tikhomirov & Lulu Qian

  2. Biology, California Institute of Technology, Pasadena, 91125, California, USA

    Philip Petersen

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

    Lulu Qian

Authors
  1. Grigory Tikhomirov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lulu Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.T. and P.P. initiated the project, designed and performed the experiments, and analysed the data; P.P. developed the software tool; G.T., P.P. and L.Q. wrote the manuscript; and L.Q. guided the project.

Corresponding author

Correspondence to Lulu Qian.

Ethics declarations

Competing interests

A provisional patent application has been filed for this work, submitted to the Office of Technology Transfer at the California Institute of Technology.

Additional information

Reviewer Information Nature thanks T. LaBean, H. Yan and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

This file contains Supplementary Materials and Methods, Supplementary Notes, Supplementary Data and Analysis (Supplementary Figures 1-23), DNA sequences (Supplementary Tables S1-S6), and additional references – see contents page for details. (PDF 17127 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tikhomirov, G., Petersen, P. & Qian, L. Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns. Nature 552, 67–71 (2017). https://doi.org/10.1038/nature24655

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature24655

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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