Letter | Published:

Complex shapes self-assembled from single-stranded DNA tiles

Nature volume 485, pages 623626 (31 May 2012) | Download Citation

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.

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References

  1. 1.

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

  2. 2.

    & DNA double-crossover molecules. Biochemistry 32, 3211–3220 (1993)

  3. 3.

    , , & Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998)

  4. 4.

    , , , & DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301, 1882–1884 (2003)

  5. 5.

    , & Algorithmic self-assembly of DNA Sierpinski triangles. PLoS Biol. 2, e424 (2004)

  6. 6.

    , & A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004)

  7. 7.

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

  8. 8.

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

  9. 9.

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

  10. 10.

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

  11. 11.

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

  12. 12.

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

  13. 13.

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

  14. 14.

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

  15. 15.

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

  16. 16.

    , & Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009)

  17. 17.

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

  18. 18.

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

  19. 19.

    , , & Crystalline two dimensional DNA origami arrays. Angew. Chem. Int. Ed. 50, 264–267 (2011)

  20. 20.

    , & Organizing DNA origami tiles into larger structures using preformed scaffold frames. Nano Lett. 11, 2997–3002 (2011)

  21. 21.

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

  22. 22.

    , , & Organization of intracellular reactions with rationally designed RNA assemblies. Science 333, 470–474 (2011)

  23. 23.

    , , & DNA tile based self-assembly: building complex nanoarchitectures. ChemPhysChem 7, 1641–1647 (2006)

  24. 24.

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

  25. 25.

    , , , & DNA origami: a quantum leap for self-assembly of complex structures. Chem. Soc. Rev. 40, 5636–5646 (2011)

  26. 26.

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

  27. 27.

    , , & Sturdier DNA nanotubes via ligation. Nano Lett. 6, 1379–1383 (2006)

  28. 28.

    , , , & 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)

  29. 29.

    , , & Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006)

  30. 30.

    , , & Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008)

  31. 31.

    , & 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)

  32. 32.

    & DNA binding to mica correlates with cationic radius: assay by atomic force microscopy. Biophys. J. 70, 1933–1939 (1996)

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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

Affiliations

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

    • Bryan Wei
    •  & Peng Yin
  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA

    • Bryan Wei
    • , Mingjie Dai
    •  & Peng Yin
  3. Program in Biophysics, Harvard University, Boston, Massachusetts 02115, USA

    • Mingjie Dai

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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.

Competing interests

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

Corresponding author

Correspondence to Peng Yin.

Supplementary information

Zip files

  1. 1.

    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.

Excel files

  1. 1.

    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.

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DOI

https://doi.org/10.1038/nature11075

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