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Placing molecules with Bohr radius resolution using DNA origami

Nature Nanotechnology volume 11, pages 47–52 (2016)Cite this article

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Abstract

Molecular self-assembly with nucleic acids can be used to fabricate discrete objects with defined sizes and arbitrary shapes1,2. It relies on building blocks that are commensurate to those of biological macromolecular machines and should therefore be capable of delivering the atomic-scale placement accuracy known today only from natural and designed proteins3,4. However, research in the field has predominantly focused on producing increasingly large and complex, but more coarsely defined, objects5,6,7,8,9,10 and placing them in an orderly manner on solid substrates11,12. So far, few objects afford a design accuracy better than 5 nm13,14,15,16, and the subnanometre scale has been reached only within the unit cells of designed DNA crystals17. Here, we report a molecular positioning device made from a hinged DNA origami object in which the angle between the two structural units can be controlled with adjuster helices. To test the positioning capabilities of the device, we used photophysical and crosslinking assays that report the coordinate of interest directly with atomic resolution. Using this combination of placement and analysis, we rationally adjusted the average distance between fluorescent molecules and reactive groups from 1.5 to 9 nm in 123 discrete displacement steps. The smallest displacement step possible was 0.04 nm, which is slightly less than the Bohr radius. The fluctuation amplitudes in the distance coordinate were also small (±0.5 nm), and within a factor of two to three of the amplitudes found in protein structures18.

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Figure 1: Concept of a high-resolution DNA positioning device.
Figure 2: Test of the positioning mechanism.
Figure 3: Positioning validation using photophysical interactions.
Figure 4: Measuring fluctuations by chemical crosslinking.

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References

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

    Article  CAS  Google Scholar 

  2. Jones, M. R., Seeman, N. C. & Mirkin, C. A. Nanomaterials. Programmable materials and the nature of the DNA bond. Science 347, 1260901 (2015).

    Article  Google Scholar 

  3. Gonen, S., DiMaio, F., Gonen, T. & Baker, D. Design of ordered two-dimensional arrays mediated by noncovalent protein–protein interfaces. Science 348, 1365–1368 (2015).

    Article  CAS  Google Scholar 

  4. King, N. P. et al. Computational design of self-assembling protein nanomaterials with atomic level accuracy. Science 336, 1171–1174 (2012).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. 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).

    Article  CAS  Google Scholar 

  10. Marchi, A. N., Saaem, I., Vogen, B. N., Brown, S. & LaBean, T. H. Toward larger DNA origami. Nano Lett. 14, 5740–5747 (2014).

    Article  CAS  Google Scholar 

  11. Kershner, R. J. et al. Placement and orientation of individual DNA shapes on lithographically patterned surfaces. Nature Nanotech. 4, 557–561 (2009).

    Article  CAS  Google Scholar 

  12. Gopinath, A. & Rothemund, P. W. Optimized assembly and covalent coupling of single-molecule DNA origami nanoarrays. ACS Nano 8, 12030–12040 (2014).

    Article  CAS  Google Scholar 

  13. Bai, X. C., Martin, T. G., Scheres, S. H. & Dietz, H. Cryo-EM structure of a 3D DNA-origami object. Proc. Natl Acad. Sci. USA 109, 20012–20017 (2012).

    Article  CAS  Google Scholar 

  14. Zhang, Z. et al. A DNA tile actuator with eleven discrete states. Angew. Chem. Int. Ed. 50, 3983–3987 (2011).

    Article  CAS  Google Scholar 

  15. Kato, T., Goodman, R. P., Erben, C. M., Turberfield, A. J. & Namba, K. High-resolution structural analysis of a DNA nanostructure by cryoEM. Nano Lett. 9, 2747–2750 (2009).

    Article  CAS  Google Scholar 

  16. Tian, C. et al. Directed self-assembly of DNA tiles into complex nanocages. Angew. Chem. Int. Ed. 53, 8041–8044 (2014).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Henzler-Wildman, K. & Kern, D. Dynamic personalities of proteins. Nature 450, 964–972 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Scheres, S. H., Nunez-Ramirez, R., Sorzano, C. O., Carazo, J. M. & Marabini, R. Image processing for electron microscopy single-particle analysis using XMIPP. Nature Protoc. 3, 977–990 (2008).

    Article  CAS  Google Scholar 

  22. Förster, T. Zwischenmolekulare energiewanderung und fluoreszenz. Ann. Phys. (Berlin) 437, 55–75 (1948).

    Article  Google Scholar 

  23. Stryer, L. Fluorescence energy transfer as a spectroscopic ruler. Annu. Rev. Biochem. 47, 819–846 (1978).

    Article  CAS  Google Scholar 

  24. Kalinin, S. et al. A toolkit and benchmark study for FRET-restrained high-precision structural modeling. Nature Methods 9, 1218–1225 (2012).

    Article  CAS  Google Scholar 

  25. Doose, S., Neuweiler, H. & Sauer, M. A close look at fluorescence quenching of organic dyes by tryptophan. ChemPhysChem 6, 2277–2285 (2005).

    Article  CAS  Google Scholar 

  26. Scheibe, G. Über die Veränderlichkeit der Absorptionsspektren in Lösungen und die Nebenvalenzen als ihre Ursachen. Angew. Chem. 50, 212–219 (1937).

    Article  CAS  Google Scholar 

  27. Fasold, H., Klappenberger, J., Meyer, C. & Remold, H. Bifunctional reagents for the crosslinking of proteins. Angew. Chem. Int. Ed. Engl. 10, 795–801 (1971).

    Article  Google Scholar 

  28. Kliche, W., Pfannstiel, J., Tiepold, M., Stoeva, S. & Faulstich, H. Thiol-specific cross-linkers of variable length reveal a similar separation of SH1 and SH2 in myosin subfragment 1 in the presence and absence of MgADP. Biochemistry 38, 10307–10317 (1999).

    Article  CAS  Google Scholar 

  29. Green, N. S., Reisler, E. & Houk, K. N. Quantitative evaluation of the lengths of homobifunctional protein cross-linking reagents used as molecular rulers. Prot. Sci. 10, 1293–1304 (2001).

    Article  CAS  Google Scholar 

  30. Li, X. & Liu, D. R. DNA-templated organic synthesis: nature's strategy for controlling chemical reactivity applied to synthetic molecules. Angew. Chem. Int. Ed. 43, 4848–4870 (2004).

    Article  CAS  Google Scholar 

  31. Gartner, Z. J. et al. DNA-templated organic synthesis and selection of a library of macrocycles. Science 305, 1601–1605 (2004).

    Article  CAS  Google Scholar 

  32. McKee, M. L. et al. Programmable one-pot multistep organic synthesis using DNA junctions. J. Am. Chem. Soc. 134, 1446–1449 (2012).

    Article  CAS  Google Scholar 

  33. Di Fiori, N. & Meller, A. The effect of dye–dye interactions on the spatial resolution of single-molecule FRET measurements in nucleic acids. Biophys. J. 98, 2265–2272 (2010).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank C. Castro for preliminary work on this project and F. Praetorius for scaffold DNA preparations. The authors also thank S. Niekamp for technical assistance. This work was supported by a European Research Council starting grant to H.D. (GA no. 256270) and by the Deutsche Forschungsgemeinschaft through grants provided within the Sonderforschungsbereich SFB863, and the Excellence Clusters CIPSM (Center for Integrated Protein Science Munich) and NIM (Nanosystems Initiative Munich).

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  1. Physik Department, Walter Schottky Institute, Technische Universität München, Am Coulombwall 4a, Garching near Munich, 85748, Germany

    Jonas J. Funke & Hendrik Dietz

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  1. Jonas J. Funke
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Contributions

J.J.F. performed the research. H.D. designed the research. J.J.F and H.D. analysed and discussed the data. J.J.F. and H.D. prepared the figures and wrote the manuscript.

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Correspondence to Hendrik Dietz.

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Funke, J., Dietz, H. Placing molecules with Bohr radius resolution using DNA origami. Nature Nanotech 11, 47–52 (2016). https://doi.org/10.1038/nnano.2015.240

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