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.

  • Article
  • Published:

Encoding signal propagation on topology-programmed DNA origami

Abstract

Biological systems often rely on topological transformation to reconfigure connectivity between nodes to guide the flux of molecular information. Here we develop a topology-programmed DNA origami system that encodes signal propagation at the nanoscale, analogous to topologically efficient information processing in cellular systems. We present a systematic molecular implementation of topological operations involving ‘glue–cut’ processes that can prompt global conformational change of DNA origami structures, with demonstrated major topological properties including genus, number of boundary components and orientability. By spatially arranging reactive DNA hairpins, we demonstrate signal propagation across transmission paths of varying lengths and orientations, and curvatures on the curved surfaces of three-dimensional origamis. These DNA origamis can also form dynamic scaffolds for regulating the spatial and temporal signal propagations whereby topological transformations spontaneously alter the location of nodes and boundary of signal propagation network. We anticipate that our strategy for topological operations will provide a general route to manufacture dynamic DNA origami nanostructures capable of performing global structural transformations under programmable control.

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

Access options

Buy this article

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

Fig. 1: Topological transformation of DNA origami systems.
Fig. 2: Design and visualization of reconfigurable topological DNA origami.
Fig. 3: Three-dimensional origamis with spheroidal or hyperboloid configuration.
Fig. 4: Signal propagation via molecular wires on the curved surface.
Fig. 5: Multipurpose dual-rail gates on the reconfigurable DNA origami.

Similar content being viewed by others

Data availability

The data and experimental protocols for this work are available within Supplementary Information and from the corresponding author on request. Supplementary Information is available in the online version of the paper. The design files and oxDNA simulation results are available at https://nanobase.org/structure/184. Source data are provided with this paper.

References

  1. Stadhouders, R., Filion, G. J. & Graf, T. Transcription factors and 3D genome conformation in cell-fate decisions. Nature 569, 345–354 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Chen, H., Li, C., Zhou, Z. & Liang, H. Fast-evolving human-specific neural enhancers are associated with aging-related diseases. Cell syst. 6, 604–611 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bullmore, E. & Sporns, O. The economy of brain network organization. Nat. Rev. Neurosci. 13, 336–349 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Bullmore, E. & Sporns, O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10, 186–198 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Dixon, J. R., Gorkin, D. U. & Ren, B. Chromatin domains: the unit of chromosome organization. Mol. Cell 65, 668–680 (2016).

    Article  Google Scholar 

  6. Sexton, T. & Cavalli, G. The role of chromosome domains in shaping the functional genome. Cell 160, 1049–1059 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Liu, P., Williams, J. R. & Cha, J. J. Topological nanomaterials. Nat. Rev. Mater. 4, 479–496 (2019).

    Article  CAS  Google Scholar 

  8. Li, L. L. et al. Intracellular construction of topology-controlled polypeptide nanostructures with diverse biological functions. Nat. Commun. 8, 1276 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Forgan, R. S., Sauvage, J. P. & Stoddart, J. F. Chemical topology: complex molecular knots, links, and entanglements. Chem. Rev. 111, 5434–5464 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Chichak, K. S. et al. Molecular borromean rings. Science 304, 1308–1312 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Schill, G. Catenanes, Rotaxanes and Knots (Academic Press, 1971).

  12. Sauvage, J. P. & Christiane, D. B. Molecular Catenanes, Rotaxanes and Knots: A Journey through the World of Molecular Topology (Wiley-VCH, 1999).

  13. Seeman, N. C. DNA in a material world. Nature 421, 427–431 (2003).

    Article  PubMed  Google Scholar 

  14. 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  PubMed  PubMed Central  Google Scholar 

  15. Chen, Y. J., Groves, B., Muscat, R. A. & Seelig, G. DNA nanotechnology from the test tube to the cell. Nat. Nanotech. 10, 748–760 (2015).

    Article  CAS  Google Scholar 

  16. Condon, A. Designed DNA molecules: principles and applications of molecular nanotechnology. Nat. Rev. Genet. 7, 565–575 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dey, S. et al. DNA origami. Nat. Rev. Methods Primers 1, 13 (2021).

    Article  Google Scholar 

  18. Liu, D., Chen, G., Akhter, U., Cronin, T. M. & Weizmann, Y. Creating complex molecular topologies by configuring DNA four-way junctions. Nat. Chem. 8, 907–914 (2016).

    Article  CAS  PubMed  Google Scholar 

  19. Kočar, V. et al. Design principles for rapid folding of knotted DNA nanostructures. Nat. Commun. 7, 10803 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bucka, A. & Stasiak, A. Construction and electrophoretic migration of single-stranded DNA knots and catenanes. Nucleic Acids Res. 30, e24 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Ramezani, H. & Dietz, H. Building machines with DNA molecules. Nat. Rev. Genet. 21, 5–26 (2020).

    Article  CAS  PubMed  Google Scholar 

  23. Qi, X. et al. Programming molecular topologies from single-stranded nucleic acids. Nat. Commun. 9, 4579 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mokhtar, R. et al. DNA Origami Transformers (DNA‐and RNA‐Based Computing Systems, 2021).

  25. Siavashpouri, M., Wachauf, C. H., Zakhary, M. J., Praetorius, F. Dietz, H. & Dogic, Z. Molecular engineering of chiral colloidal liquid crystals using DNA origami. Nat. Mater. 16, 849–856 (2017).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  28. Goodman, R. P. et al. Reconfigurable, braced, three-dimensional DNA nanostructures. Nat. Nanotech. 3, 93–96 (2008).

    Article  CAS  Google Scholar 

  29. Zhang, Z., Yang, Y., Pincet, F., Llaguno, M. C. & Lin, C. Placing and shaping liposomes with reconfigurable DNA nanocages. Nat. Chem. 9, 653–659 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Han, D., Pal, S., Liu, Y. & Yan, H. Folding and cutting DNA into reconfigurable topological nanostructures. Nat. Nanotech. 5, 712–717 (2010).

    Article  CAS  Google Scholar 

  31. 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  PubMed  PubMed Central  Google Scholar 

  32. Li, J. et al. Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat. Nat. Nanotechnol. 13, 723–729 (2018).

    Article  CAS  PubMed  Google Scholar 

  33. 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. 116, 5014–5019 (2004).

    Article  Google Scholar 

  34. Stupka, I. et al. Chemically induced protein cage assembly with programmable opening and cargo release. Sci. Adv. 8, eabj9424 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liu, M. et al. A DNA tweezer-actuated enzyme nanoreactor. Nat. Commun. 4, 1–5 (2013).

    Google Scholar 

  36. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Bohlin, J. et al. Design and simulation of DNA, RNA and hybrid protein–nucleic acid nanostructures with oxView. Nat. Protoc. 17, 1762–1788 (2022).

    Article  CAS  PubMed  Google Scholar 

  42. Poppleton, E. et al. Design, optimization and analysis of large DNA and RNA nanostructures through interactive visualization, editing and molecular simulation. Nucleic Acids Res. 12, e72–e72 (2020).

    Article  Google Scholar 

  43. Poppleton, E. et al. oxDNA.org: a public webserver for coarse-grained simulations of DNA and RNA nanostructures. Nucleic Acids Res. 49, W491–W498 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Suma, A. et al. Tacoxdna: a user‐friendly web server for simulations of complex DNA structures, from single strands to origami. J. Comput. Chem. 40, 2586–2595 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. Sengar, A. et al. A primer on the oxDNA model of DNA: when to use it, how to simulate it and how to interpret the results. Front. Mol. Biosci. 8, 693710 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  47. Chao, J. et al. Solving mazes with single-molecule DNA navigators. Nat. Mater. 18, 273–279 (2019).

    Article  CAS  PubMed  Google Scholar 

  48. Fan, S. et al. Proximity-induced pattern operations in reconfigurable DNA origami domino array. J. Am. Chem. Soc. 142, 14566–14573 (2020).

    Article  CAS  PubMed  Google Scholar 

  49. Bui, H. et al. Localized DNA hybridization chain reactions on DNA origami. ACS Nano 12, 1146–1155 (2018).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. Kim, D. N., Kilchherr, F., Dietz, H. & Bathe, M. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures. Nucleic Acids Res. 40, 2862–2868 (2012).

    Article  CAS  PubMed  Google Scholar 

  53. Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graphics 14, 33–38 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We express our gratitude to Y. Zou from the Department of Mathematics at East China Normal University for his valuable contributions to our discussions on the topology of DNA origamis. This work was supported by the National Science Foundation of China (grant nos. T2188102 and 21991134), the National Key R&D Program of China (2021YFF1200300), the Shanghai Science and Technology Committee (STCSM) (23ZR1479600) and the New Cornerstone Science Foundation.

Author information

Authors and Affiliations

Authors

Contributions

H.P. and C.F. conceived and supervised the project. W.J. designed and performed the experiments. M.C. and Y.Z. conducted the origami synthesis as well as the AFM and PAGE analyses. X.X., M.C. and Y.Z. carried out the oxDNA simulations. H.P., W.J., X.X., C.F. and M.C. discussed the design. All authors contributed to data analysis and interpretation. X.X., L.L., M.C., Y.Z. C.F. and H.P. wrote the paper.

Corresponding authors

Correspondence to Chunhai Fan or Hao Pei.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Chemistry thanks Ebbe Andersen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

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

Supplementary information

Supplementary Information

Supplementary Figs. 1–33, discussion and Table 1.

Supplementary Table 1

DNA sequences.

Supplementary Data 1

Source data for supplementary figures.

Supplementary Video 1

A video file showing the oxDNA simulated structures of 3D cross-link H.

Supplementary Video 2

A video file showing the oxDNA simulated structures of 3D cross-link S.

Supplementary Video 3

A video file showing the oxDNA simulated structures of 3D deformed figure-eight H.

Supplementary Video 4

A video file showing the oxDNA simulated structures of 3D deformed figure-eight S.

Supplementary Video 5

A video file showing the oxDNA simulated structures of 3D Möbius-shorts H.

Supplementary Video 6

A video file showing the oxDNA simulated structures of 3D Möbius-shorts S.

Source data

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ji, W., Xiong, X., Cao, M. et al. Encoding signal propagation on topology-programmed DNA origami. Nat. Chem. (2024). https://doi.org/10.1038/s41557-024-01565-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41557-024-01565-2

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