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Self-assembling DNA nanotubes to connect molecular landmarks

Nature Nanotechnology volume 12, pages 312–316 (2017)Cite this article

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Abstract

Within cells, nanostructures are often organized using local assembly rules that produce long-range order1,2. Because these rules can take into account the cell's current structure and state, they can enable complexes, organelles or cytoskeletal structures to assemble around existing cellular components to form architectures3,4,5,6. Although many methods for self-assembling biomolecular nanostructures have been developed7,8,9,10,11, few can be programmed to assemble structures whose form depends on the identity and organization of structures already present in the environment. Here, we demonstrate that DNA nanotubes can grow to connect pairs of molecular landmarks with different separation distances and relative orientations. DNA tile nanotubes nucleate at these landmarks and grow while their free ends diffuse. The nanotubes can then join end to end to form stable connections, with unconnected nanotubes selectively melted away. Connections form between landmark pairs separated by 1–10 µm in more than 75% of cases and can span a surface or three dimensions. This point-to-point assembly process illustrates how self-assembly kinetics can be designed to produce structures with a desired physical property rather than a specific shape.

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Figure 1: Scheme for assembling interconnects between fixed molecular landmarks and the DNA nanostructures used within the assembly process.
Figure 2: DNA nanotubes connecting molecular landmarks.
Figure 3: Model calibrated using measured nanotube growth rates, and rotational and translational diffusion constants that reproduces the connection yields from experiment.
Figure 4: Assembly of DNA nanotube interconnects in three dimensions and selective melting of unconnected nanotubes.

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Acknowledgements

The authors thank D. Fygenson, M. Bevan, D. Gracias, E. Winfree, D. Agrawal, S. Schaffter and E. Franco for discussions and advice on the manuscript, J. Liphardt for the use of equipment and advice, and J. Fern, E. Pryce, R. Zuckermann and C. Ajo-Franklin for technical advice. This research has been supported by DOE grant DE-SC0010595, which provided money for materials, supplies and computing time, NSF CAREER award 125387, and the Miller Institute for Basic Science. P.Š. is supported by a grant from the Simons Foundation. Preliminary work related to this project at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy, under contract no. DE-AC02-05CH11231.

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Authors and Affiliations

  1. Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, 21218, Maryland, USA

    Abdul M. Mohammed, John Zenk & Rebecca Schulman

  2. Center for Studies in Physics and Biology, The Rockefeller University, New York, 10065, New York, USA

    Petr Šulc

  3. Computer Science, Johns Hopkins University, Baltimore, 21218, Maryland, USA

    Rebecca Schulman

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  1. Abdul M. Mohammed
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  2. Petr Šulc
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Contributions

A.M.M. and R.S. designed the experiments and carried out the experimental analysis. A.M.M. conducted the experiments. P.Š. and R.S. designed the simulations. P.Š. and J.Z. developed simulations and analysed simulation results. All the authors discussed the results and wrote the manuscript.

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Correspondence to Rebecca Schulman.

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The authors declare no competing financial interests.

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Mohammed, A., Šulc, P., Zenk, J. et al. Self-assembling DNA nanotubes to connect molecular landmarks. Nature Nanotech 12, 312–316 (2017). https://doi.org/10.1038/nnano.2016.277

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