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.

  • Letter
  • Published:

Complex shapes self-assembled from single-stranded DNA tiles

Nature volume 485, pages 623–626 (2012)Cite this article

Subjects

Abstract

Programmed self-assembly of strands of nucleic acid has proved highly effective for creating a wide range of structures with desired shapes1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25. A particularly successful implementation is DNA origami, in which a long scaffold strand is folded by hundreds of short auxiliary strands into a complex shape9,14,15,16,18,19,20,21,25. Modular strategies are in principle simpler and more versatile and have been used to assemble DNA2,3,4,5,8,10,11,12,13,17,23 or RNA7,22 tiles into periodic3,4,7,22 and algorithmic5 two-dimensional lattices, extended ribbons10,12 and tubes4,12,13, three-dimensional crystals17, polyhedra11 and simple finite two-dimensional shapes7,8. But creating finite yet complex shapes from a large number of uniquely addressable tiles remains challenging. Here we solve this problem with the simplest tile form, a ‘single-stranded tile’ (SST) that consists of a 42-base strand of DNA composed entirely of concatenated sticky ends and that binds to four local neighbours during self-assembly12. Although ribbons and tubes with controlled circumferences12 have been created using the SST approach, we extend it to assemble complex two-dimensional shapes and tubes from hundreds (in some cases more than one thousand) distinct tiles. Our main design feature is a self-assembled rectangle that serves as a molecular canvas, with each of its constituent SST strands—folded into a 3 nm-by-7 nm tile and attached to four neighbouring tiles—acting as a pixel. A desired shape, drawn on the canvas, is then produced by one-pot annealing of all those strands that correspond to pixels covered by the target shape; the remaining strands are excluded. We implement the strategy with a master strand collection that corresponds to a 310-pixel canvas, and then use appropriate strand subsets to construct 107 distinct and complex two-dimensional shapes, thereby establishing SST assembly as a simple, modular and robust framework for constructing nanostructures with prescribed shapes from short synthetic DNA strands.

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: Self-assembly of molecular shapes using single-stranded tiles.
Figure 2: Self-assembly of SST rectangles and tubes.
Figure 3: Simple shapes designed using a molecular canvas.
Figure 4: Complex shapes designed using a molecular canvas.

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Fu, T. J. & Seeman, N. C. DNA double-crossover molecules. Biochemistry 32, 3211–3220 (1993)

    Article  CAS  Google Scholar 

  3. Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998)

    Article  ADS  CAS  Google Scholar 

  4. Yan, H., Park, S. H., Finkelstein, G., Reif, J. H. & LaBean, T. H. DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301, 1882–1884 (2003)

    Article  ADS  CAS  Google Scholar 

  5. Rothemund, P. W. K., Papadakis, N. & Winfree, E. Algorithmic self-assembly of DNA Sierpinski triangles. PLoS Biol. 2, e424 (2004)

    Article  Google Scholar 

  6. Shih, W., Quispe, J. & Joyce, G. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004)

    Article  ADS  CAS  Google Scholar 

  7. Chworos, A. et al. Building programmable jigsaw puzzles with RNA. Science 306, 2068–2072 (2004)

    Article  ADS  CAS  Google Scholar 

  8. Park, S. H. et al. Finite-size, fully-addressable DNA tile lattices formed by hierarchical assembly procedures. Angew. Chem. Int. Ed. 45, 735–739 (2006)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  10. Schulman, R. & Winfree, E. Synthesis of crystals with a programmable kinetic barrier to nucleation. Proc. Natl Acad. Sci. USA 104, 15236–15241 (2007)

    Article  ADS  CAS  Google Scholar 

  11. He, Y. et al. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452, 198–201 (2008)

    Article  ADS  CAS  Google Scholar 

  12. Yin, P. et al. Programming DNA tube circumferences. Science 321, 824–826 (2008)

    Article  ADS  CAS  Google Scholar 

  13. Sharma, J. et al. Control of self-assembly of DNA tubules through integration of gold nanoparticles. Science 323, 112–116 (2009)

    Article  ADS  CAS  Google Scholar 

  14. Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009)

    Article  ADS  CAS  Google Scholar 

  15. Andersen, E. S. et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73–76 (2009)

    Article  ADS  CAS  Google Scholar 

  16. Dietz, H., Douglas, S. M. & Shih, W. M. Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009)

    Article  ADS  CAS  Google Scholar 

  17. Zheng, J. P. et al. From molecular to macroscopic via the rational design of self-assembled 3D DNA crystal. Nature 461, 74–77 (2009)

    Article  ADS  CAS  Google Scholar 

  18. Han, D. et al. DNA origami with complex curvatures in three-dimensional space. Science 332, 342–346 (2011)

    Article  ADS  CAS  Google Scholar 

  19. Liu, W., Zhong, H., Wang, R. & Seeman, N. Crystalline two dimensional DNA origami arrays. Angew. Chem. Int. Ed. 50, 264–267 (2011)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Delebecque, C. J., Lindner, A. B., Silver, P. A. & Aldaye, F. A. Organization of intracellular reactions with rationally designed RNA assemblies. Science 333, 470–474 (2011)

    Article  ADS  CAS  Google Scholar 

  23. Lin, C., Liu, Y., Rinker, S. & Yan, H. DNA tile based self-assembly: building complex nanoarchitectures. ChemPhysChem 7, 1641–1647 (2006)

    Article  CAS  Google Scholar 

  24. Seeman, N. Nanomaterials based on DNA. Annu. Rev. Biochem. 79, 65–87 (2010)

    Article  CAS  Google Scholar 

  25. Tørring, T., Voigt, N. V., Nangreave, J., Yan, H. & Gothelf, K. V. DNA origami: a quantum leap for self-assembly of complex structures. Chem. Soc. Rev. 40, 5636–5646 (2011)

    Article  Google Scholar 

  26. Seeman, N. De novo design of sequences for nucleic acid structural engineering. J. Biomol. Struct. Dyn. 8, 573–581 (1990)

    Article  CAS  Google Scholar 

  27. O’Neill, P., Rothemund, P. W. K., Kumar, A. & Fygenson, D. Sturdier DNA nanotubes via ligation. Nano Lett. 6, 1379–1383 (2006)

    Article  ADS  Google Scholar 

  28. Rajendran, A., Endo, M., Katsuda, Y., Hidaka, K. & Sugiyama, H. Photo-crosslinking-assisted thermal stability of DNA origami structures and its application for higher-temperature self-assembly. J. Am. Chem. Soc. 133, 14488–14491 (2011)

    Article  CAS  Google Scholar 

  29. Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006)

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  31. Wei, B., Wang, Z. & Mi, Y. Uniquimer: software of de novo DNA sequence generation for DNA self-assembly: an introduction and the related applications in DNA self-assembly. J. Comput. Theor. Nanosci. 4, 133–141 (2007)

    CAS  Google Scholar 

  32. Hansma, H. G. & Laney, D. E. DNA binding to mica correlates with cationic radius: assay by atomic force microscopy. Biophys. J. 70, 1933–1939 (1996)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank S. Chandarasekaran, X. Lim, W. Sun and R. Conturie for technical assistance; A. Marblestone, R. Barish, W. Shih, Y. Ke, E. Winfree, S. Woo, P. Rothemund and D. Woods for discussions; and J. Aliperti for help with preparation of the draft. This work was funded by Office of Naval Research Young Investigator Program Award N000141110914, Office of Naval Research Grant N000141010827, NSF CAREER Award CCF1054898, NIH Director’s New Innovator Award 1DP2OD007292 and a Wyss Institute for Biologically Inspired Engineering Faculty Startup Fund (to P.Y.).

Author information

Authors and Affiliations

  1. Department of Systems Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Bryan Wei & Peng Yin

  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 02115, Massachusetts, USA

    Bryan Wei, Mingjie Dai & Peng Yin

  3. Program in Biophysics, Harvard University, Boston, 02115, Massachusetts, USA

    Mingjie Dai

Authors
  1. Bryan Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingjie Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.W. designed the system, conducted the experiments, analysed the data and wrote the paper. M.D. conducted the experiments, analysed the data and wrote the paper. P.Y. conceived and guided the study, analysed the data and wrote the paper.

Corresponding author

Correspondence to Peng Yin.

Ethics declarations

Competing interests

The authors declare competing financial interests in the form of a pending provisional patent.

Supplementary information

Supplementary Information

This folder contains 3 files. The file “Supplementary-Information-s1-s5” (Primary information) is the primary supplementary information file, and contains details of system design, experimental results, data analysis, and discussions. The file “sup-1.info.s6” (Diagrams) shows schematics of rectangles across scales, tubes across scale and four sets of edge protectors are shown on pages 2, 3 and 4 respectively. In order to see the segment names properly, one should print the file with a minimal size of 11×17 inches, 34×11 inches and 11×17 inches respectively for pages 2, 3 and 4. The file “Sup.info.s7” (Sequences and lists) contains firstly Sequence information of the structures in the paper and secondly lists of the names of the constituent strands for different shapes constructed from the molecular canvas. (ZIP 14311 kb)

Supplementary Table S8

The file contains sequence information of the structures in the paper. The sequence information is identical as the first part of Supplementary Information S7, but is presented in Excel format, and is easier to retrieve for a reader who wants to repeat the experiments described in the paper. (XLS 539 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012). https://doi.org/10.1038/nature11075

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11075

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