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

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.

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

References

  1. 1

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

    CAS  Article  Google Scholar 

  2. 2

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

    CAS  ADS  Article  Google Scholar 

  3. 3

    Gu, H., Chao, J., Xiao, S.-J. & Seeman, N. C. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010)

    CAS  ADS  Article  Google Scholar 

  4. 4

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

    CAS  ADS  Article  Google Scholar 

  5. 5

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

    Article  Google Scholar 

  6. 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)

    CAS  ADS  Article  Google Scholar 

  7. 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)

    CAS  ADS  Article  Google Scholar 

  8. 8

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

    CAS  ADS  Article  Google Scholar 

  9. 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)

    CAS  ADS  Article  Google Scholar 

  10. 10

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

    CAS  ADS  Article  Google Scholar 

  11. 11

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

    CAS  Article  Google Scholar 

  12. 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)

    CAS  Article  Google Scholar 

  13. 13

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

    CAS  ADS  Article  Google Scholar 

  14. 14

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

    CAS  ADS  Article  Google Scholar 

  15. 15

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

    CAS  ADS  Article  Google Scholar 

  16. 16

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

    Article  Google Scholar 

  17. 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. 18

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

    CAS  ADS  Article  Google Scholar 

  19. 19

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

  20. 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)

    CAS  ADS  Article  Google Scholar 

  21. 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)

    CAS  Article  Google Scholar 

  22. 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)

    CAS  ADS  Article  Google Scholar 

  23. 23

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

    CAS  Article  Google Scholar 

  24. 24

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

  25. 25

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

  26. 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)

    CAS  Article  Google Scholar 

  27. 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)

    CAS  Article  Google Scholar 

  28. 28

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

    CAS  ADS  Article  Google Scholar 

  29. 29

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

    Article  Google Scholar 

  30. 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. 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).

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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.

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

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

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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)

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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

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