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Design and operation of reconfigurable two-dimensional DNA molecular arrays


Information relay and cascaded transformation are essential in biology and engineering. Imitation of such complex behaviors via synthetic molecular self-assembly at the nanoscale remains challenging. Here we describe the use of structural DNA nanotechnology to realize prescribed, multistep, long-range information relay and cascaded transformation in rationally designed molecular arrays. The engineered arrays provide a controlled platform for studying complex dynamic behaviors of molecular arrays and have a range of potential applications, such as with reconfigurable metamaterials. A reconfigurable array consists of a prescribed number of interconnected dynamic DNA antijunctions. Each antijunction unit consists of four DNA domains of equal length with four dynamic nicking points, which are capable of switching between two stable conformations through an intermediate open conformation. By interconnecting the small DNA antijunctions, one can build custom two-dimensional (2D) molecular ‘domino’ arrays with arbitrary shapes. More important, the DNA molecular arrays are capable of undergoing programmed, multistep, long-range transformation driven by information relay between neighboring antijunction units. The information relay is initiated by the trigger strands under high temperature or formamide concentration. The array’s dynamic behavior can be regulated by external factors such as its shape and size, points of transformation initiation, and/or any engineered information propagation pathways. This protocol provides detailed strategies for designing DNA molecular arrays, as well as procedures for sample production, purification, reconfiguration, and imaging by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The procedure can be completed in 4–7 d.

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Fig. 1: Dynamic DNA antijunction and reconfiguration of DNA arrays driven by trigger strands and information relay through antijunction units.
Fig. 2
Fig. 3: Design of DNA antijunctions and DNA arrays.
Fig. 4: Overview of sample preparation for DNA brick or origami molecular arrays.
Fig. 5: AFM imaging process for in situ transformation.
Fig. 6: Regulation strategies for DNA origami relay arrays.


  1. 1.

    Park, S. H. et al. Three-helix bundle DNA tiles self-assemble into 2D lattice or 1D templates for silver nanowires. Nano Lett. 5, 693–696 (2005).

    CAS  Article  Google Scholar 

  2. 2.

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

    CAS  Article  Google Scholar 

  3. 3.

    Aldaye, F. A., Palmer, A. L. & Sleiman, H. F. Assembling materials with DNA as the guide. Science 321, 1795–1799 (2008).

    CAS  Article  Google Scholar 

  4. 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).

    CAS  Article  Google Scholar 

  5. 5.

    Liu, D., Park, S. H., Reif, J. H. & LaBean, T. H. DNA nanotubes self-assembled from triple-crossover tiles as templates for conductive nanowires. Proc. Natl. Acad. Sci. USA 101, 717–722 (2004).

    CAS  Article  Google Scholar 

  6. 6.

    Rothemund, P. W. K. et al. Design and characterization of programmable DNA nanotubes. J. Am. Chem. Soc. 126, 16344–16352 (2004).

    CAS  Article  Google Scholar 

  7. 7.

    Mathieu, F. et al. Six-helix bundles designed from DNA. Nano Lett. 5, 661–665 (2005).

    CAS  Article  Google Scholar 

  8. 8.

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

    CAS  Article  Google Scholar 

  9. 9.

    Ke, Y. et al. DNA brick crystals with prescribed depths. Nat. Chem. 6, 994–1002 (2014).

    CAS  Article  Google Scholar 

  10. 10.

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

    CAS  Article  Google Scholar 

  11. 11.

    Rothemund, P. W. K., Papadakis, N. & Winfree, E. Algorithmic self-assembly of DNA Sierpinski triangles. PLoS Biol. 2, 2041–2053 (2004).

    CAS  Article  Google Scholar 

  12. 12.

    He, Y. et al. Sequence symmetry as a tool for designing DNA nanostructures. Angew. Chem. Int. Ed. 117, 6852–6854 (2005).

    Article  Google Scholar 

  13. 13.

    Gerling, T., Wagenbauer, K. F., Neuner, A. M. & Dietz, H. Dynamic DNA devices and assemblies formed by shape-complementary, non-base pairing 3D components. Science 347, 1446–1452 (2015).

    CAS  Article  Google Scholar 

  14. 14.

    Wang, P. et al. Programming self-assembly of DNA origami honeycomb two-dimensional lattices and plasmonic metamaterials. J. Am. Chem. Soc. 138, 7733–7740 (2016).

    CAS  Article  Google Scholar 

  15. 15.

    Liu, W., Halverson, J., Tian, Y., Tkachenko, A. V. & Gang, O. Self-organized architectures from assorted DNA-framed nanoparticles. Nat. Chem. 8, 867–873 (2016).

    CAS  Article  Google Scholar 

  16. 16.

    Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–627 (2012).

    CAS  Article  Google Scholar 

  17. 17.

    Chen, J. H. & Seeman, N. C. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350, 631–633 (1991).

    CAS  Article  Google Scholar 

  18. 18.

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

    CAS  Article  Google Scholar 

  19. 19.

    Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).

    CAS  Article  Google Scholar 

  20. 20.

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

    CAS  Article  Google Scholar 

  21. 21.

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

    CAS  Article  Google Scholar 

  22. 22.

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

    CAS  Article  Google Scholar 

  23. 23.

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

    CAS  Article  Google Scholar 

  24. 24.

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

    CAS  Article  Google Scholar 

  25. 25.

    Ke, Y., Ong, L. L., Shih, W. M. & Yin, P. Three-dimensional structures self-assembled from DNA bricks. Science 338, 1177–1183 (2012).

    CAS  Article  Google Scholar 

  26. 26.

    Iinuma, R. et al. Polyhedra self-assembled from DNA tripods and characterized with 3D DNA-PAINT. Science 344, 65–69 (2014).

    CAS  Article  Google Scholar 

  27. 27.

    Benson, E. et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441–444 (2015).

    CAS  Article  Google Scholar 

  28. 28.

    Veneziano, R. et al. DNA nanotechnology designer nanoscale DNA assemblies programmed from the top down. Science 352, aaf4388 (2016).

    Article  Google Scholar 

  29. 29.

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

    CAS  Article  Google Scholar 

  30. 30.

    Ke, Y., Castro, C. & Choi, J. H. Structural DNA nanotechnology: artificial nanostructures for biomedical research. Annu. Rev. Biomed. Eng. 20, 375–401 (2018).

  31. 31.

    Wang, P. et al. Practical aspects of structural and dynamic DNA nanotechnology. MRS Bull. 42, 889–896 (2017).

    CAS  Article  Google Scholar 

  32. 32.

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

    CAS  Article  Google Scholar 

  33. 33.

    Wang, P., Meyer, T. A., Pan, V., Dutta, P. K. & Ke, Y. The beauty and utility of DNA origami. Chem 2, 359–382 (2017).

    CAS  Article  Google Scholar 

  34. 34.

    Yurke, B., Turberfield, A. J., Mills, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).

    CAS  Article  Google Scholar 

  35. 35.

    Yan, H., Zhang, X. P., Shen, Z. Y. & Seeman, N. C. A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62–65 (2002).

    CAS  Article  Google Scholar 

  36. 36.

    Liu, M. et al. A DNA tweezer-actuated enzyme nanoreactor. Nat. Commun. 4, 2127 (2013).

    Article  Google Scholar 

  37. 37.

    Ke, Y. et al. Regulation at a distance of biomolecular interactions using a DNA origami nanoactuator. Nat. Commun. 7, 10935 (2016).

    CAS  Article  Google Scholar 

  38. 38.

    Kuzyk, A. et al. Reconfigurable 3D plasmonic metamolecules. Nat. Mater. 13, 862 (2014).

    CAS  Article  Google Scholar 

  39. 39.

    Kuzyk, A. et al. A light-driven three-dimensional plasmonic nanosystem that translates molecular motion into reversible chiroptical function. Nat. Commun. 7, 10591 (2016).

    CAS  Article  Google Scholar 

  40. 40.

    Sherman, W. B. & Seeman, N. C. A precisely controlled DNA biped walking device. Nano Lett. 4, 1203–1207 (2004).

    CAS  Article  Google Scholar 

  41. 41.

    Yin, P., Yan, H., Daniell, X. G., Turberfield, A. J. & Reif, J. H. A unidirectional DNA walker that moves autonomously along a track. Angew. Chem. Int. Ed. 43, 4906–4911 (2004).

    CAS  Article  Google Scholar 

  42. 42.

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

    CAS  Article  Google Scholar 

  43. 43.

    Yin, P. et al. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

    CAS  Article  Google Scholar 

  44. 44.

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

    CAS  Article  Google Scholar 

  45. 45.

    Wickham, S. F. J. et al. Direct observation of stepwise movement of a synthetic molecular transporter. Nat. Nanotechnol. 6, 166–169 (2011).

    CAS  Article  Google Scholar 

  46. 46.

    Zhou, C., Duan, X. & Liu, N. A plasmonic nanorod that walks on DNA origami. Nat. Commun. 6, 8102 (2015).

    CAS  Article  Google Scholar 

  47. 47.

    Marras, A. E., Zhou, L., Su, H.-J. & Castro, C. E. Programmable motion of DNA origami mechanisms. Proc. Natl. Acad. Sci. USA 112, 713 (2015).

    CAS  Article  Google Scholar 

  48. 48.

    Endo, M. et al. Helical DNA origami tubular structures with various sizes and arrangements. Angew. Chem, Int. Ed. 53, 7484–7490 (2014).

    CAS  Article  Google Scholar 

  49. 49.

    Song, J. et al. Reconfiguration of DNA molecular arrays driven by information relay. Science 357, eaan3377 (2017).

    Article  Google Scholar 

  50. 50.

    Du, S. M., Zhang, S. W. & Seeman, N. C. DNA junctions, antijunctions, and mesojunctions. Biochemistry 31, 10955–10963 (1992).

    CAS  Article  Google Scholar 

  51. 51.

    Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 37, 5001–5006 (2009).

    CAS  Article  Google Scholar 

  52. 52.

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

    CAS  Article  Google Scholar 

  53. 53.

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

    CAS  Article  Google Scholar 

  54. 54.

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

    Article  Google Scholar 

  55. 55.

    Choi, Y., Choi, H., Lee, A. C., Lee, H. & Kwon, S. A reconfigurable DNA accordion rack. Angew. Chem. Int. Ed. 57, 2811–2815 (2018).

    CAS  Article  Google Scholar 

  56. 56.

    Sobczak, J.-P. J., Martin, T. G., Gerling, T. & Dietz, H. Rapid folding of DNA into nanoscale shapes at constant temperature. Science 338, 1458–1461 (2012).

    CAS  Article  Google Scholar 

  57. 57.

    Bellot, G., McClintock, M. A., Chou, J. J. & Shih, W. M. DNA nanotubes for NMR structure determination of membrane proteins. Nat. Protoc. 8, 755–770 (2013).

    Article  Google Scholar 

  58. 58.

    Stahl, E., Martin, T. G., Praetorius, F. & Dietz, H. Facile and scalable preparation of pure and dense DNA origami solutions. Angew. Chem. Int. Ed. 53, 12735–12740 (2014).

    CAS  Article  Google Scholar 

  59. 59.

    Blake, R. D. & Delcourt, S. G. Thermodynamic effects of formamide on DNA stability. Nucleic Acids Res. 24, 2095–2103 (1996).

    CAS  Article  Google Scholar 

  60. 60.

    Fischer, S. G. & Lerman, L. S. DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: correspondence with melting theory. Proc. Natl. Acad. Sci. USA 80, 1579–1583 (1983).

    CAS  Article  Google Scholar 

  61. 61.

    McConaughy, B. L., Laird, C. D. & McCarthy, B. J. Nucleic acid reassociation in formamide. Biochemistry 8, 3289–3295 (1969).

    CAS  Article  Google Scholar 

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This work was supported by the NSF (CAREER Award DMR-1654485), the Wallace H. Coulter Department of Biomedical Engineering Startup Fund, a Billi and Bernie Marcus Research Award (to Y.K.), the National Natural Scientific Foundation of China (grants 11761141006 and 21605102 to J.S.), and the National Key Research and Development Program of China (grant 2017FYA0205301 to D.C.).

Author information




J.S. and Y.K. conceived and led the project. J.S., P.W., and Y.K. designed and conducted the experiments. D.W., J.S., P.W., V.P., Y.Z., D.C., and Y.K. contributed to the writing of the manuscript.

Corresponding authors

Correspondence to Jie Song or Daxiang Cui or Yonggang Ke.

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Competing interests

A provisional US patent application based on the work described in this paper has been filed.

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Article describing the development of the approach

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Integrated supplementary information

Supplementary Figure 1

Design diagram of the 11 × 4 52-bp DNA origami array.

Supplementary Figure 2

Design diagram of the 20 × 8 42-bp DNA brick array.

Supplementary information

Supplementary Figures 1 and 2 and Supplementary Tables 1 and 2

Reporting Summary

Supplementary Data 1

Python code for sequence generation

Supplementary Data 2

caDNAno files for the 11 × 4 52-bp DNA origami array and the 20 × 8 42-bp DNA brick array

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Wang, D., Song, J., Wang, P. et al. Design and operation of reconfigurable two-dimensional DNA molecular arrays. Nat Protoc 13, 2312–2329 (2018).

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