From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal (original) (raw)

Nature volume 461, pages 74–77 (2009)Cite this article

Abstract

We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter1. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends2. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so3; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 Å resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle4. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

Accession codes

Primary accessions

Protein Data Bank

References

  1. Whitesides, G. M., Mathias, J. P. & Seto, C. T. Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures. Science 254, 1312–1319 (1991)
    Article ADS CAS Google Scholar
  2. Seeman, N. C. Nucleic acid junctions and crystal formation. J. Biomol. Struct. Dyn. 3, 11–34 (1985)
    Article CAS Google Scholar
  3. Qiu, H., Dewan, J. C. & Seeman, N. C. A DNA decamer with a sticky end: the crystal structure of d-CGACGATCGT. J. Mol. Biol. 267, 881–898 (1997)
    Article CAS Google Scholar
  4. Liu, D., Wang, W., Deng, Z., Walulu, R. & Mao, C. Tensegrity: construction of rigid DNA triangles with flexible four-arm junctions. J. Am. Chem. Soc. 126, 2324–2325 (2004)
    Article CAS Google Scholar
  5. Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998)
    Article ADS CAS Google Scholar
  6. Nykypanchuk, D. M. M., Maye, M. M., van der Lelie, D. & Gang, O. DNA-guided crystallization of colloidal nanoparticles. Nature 451, 549–552 (2008)
    Article ADS CAS Google Scholar
  7. Park, S. Y. et al. DNA-programmable nanoparticle crystallization. Nature 451, 553–556 (2008)
    Article ADS CAS Google Scholar
  8. Vargason, J. M., Henderson, K. & Ho, P. S. A crystallographic map of the transition from B-DNA to A-DNA. Proc. Natl Acad. Sci. USA 98, 7265–7270 (2001)
    Article ADS CAS Google Scholar
  9. Eichmann, B. F., Vargason, J. M., Mooers, B. H. M. & Ho, P. S. The Holliday junction in an inverted repeat DNA sequence: sequence effects on the structure of four-way junctions. Proc. Natl Acad. Sci. USA 97, 3971–3976 (2000)
    Article ADS Google Scholar
  10. Mao, C., Sun, W. & Seeman, N. C. Designed two-dimensional DNA Holliday junction arrays visualized by atomic force microscopy. J. Am. Chem. Soc. 121, 5437–5443 (1999)
    Article CAS Google Scholar
  11. Sha, R., Liu, F. & Seeman, N. C. Atomic force measurement of the inter-domain angle in symmetric Holliday junctions. Biochemistry 41, 5950–5955 (2002)
    Article CAS Google Scholar
  12. Birac, J. J., Sherman, W. B., Kopatsch, J., Constantinou, P. E. & Seeman, N. C. GIDEON, a program for design in structural DNA nanotechnology. J. Mol. Graph. Model. 25, 470–480 (2006)
    Article CAS Google Scholar
  13. Paukstelis, P. J., Nowakowski, J., Birktoft, J. J. & Seeman, N. C. The crystal structure of a continuous three-dimensional DNA lattice. Chem. Biol. 11, 1119–1126 (2004)
    Article CAS Google Scholar
  14. Paukstelis, P. J. Three dimensional DNA crystals as molecular sieves. J. Am. Chem. Soc. 128, 6794–6795 (2006)
    Article CAS Google Scholar
  15. Furukawa, H., Kim, H. J., Ockwig, N. W., O’Keeffe, M. & Yaghi, O. M. Control of vertex geometry, structure dimensionality, functionality, and pore metrics in the reticular synthesis of crystalline metal-organic frameworks and polyhedra. J. Am. Chem. Soc. 130, 11650–11651 (2008)
    Article CAS Google Scholar
  16. Kawano, M., Kawamichi, T., Haneda, T., Kajima, T. & Fujita, M. The modular synthesis of functional porous coordination networks. J. Am. Chem. Soc. 129, 15418–15419 (2007)
    Article CAS Google Scholar
  17. Ding, B. & Seeman, N. C. Operation of a DNA robot arm inserted into a 2D DNA crystalline substrate. Science 314, 1583–1585 (2006)
    Article ADS CAS Google Scholar
  18. Zheng, J. et al. 2D nanoparticle arrays show the organizational power of robust DNA motifs. Nano Lett. 6, 1502–1504 (2006)
    Article ADS CAS Google Scholar
  19. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982)
    Article CAS Google Scholar
  20. Robinson, B. H. & Seeman, N. C. The design of a biochip: a self-assembling molecular-scale memory device. Protein Eng. 1, 295–300 (1987)
    Article CAS Google Scholar
  21. Gu, H., Chao, J., Xiao, S.-J. & Seeman, N. C. Dynamic patterns programmed by DNA tiles captured on a DNA origami substrate. Nature Nanotech. 4, 245–249 (2009)
    Article ADS CAS Google Scholar
  22. Rothemund, P. W. K., Papadakis, N. & Winfree, E. Algorithmic self-assembly of DNA Sierpinski triangles. PLoS Biol. 2, 2041–2053 (2004)
    Article CAS Google Scholar
  23. Seeman, N. C. De novo design of sequences for nucleic acid structure engineering. J. Biomol. Struct. Dyn. 8, 573–581 (1990)
    Article CAS Google Scholar
  24. Rosenbaum, G. et al. The Structural Biology Center 19ID undulator beamline: facility specifications and protein crystallographic results. J. Synchrotron Radiat. 13, 30–45 (2006)
    Article CAS Google Scholar

Download references

Acknowledgements

This research has been supported by grants to N.C.S. from the National Institute of General Medical Sciences, the National Science Foundation, the Army Research Office, the Office of Naval Research and the W. M. Keck Foundation. It has also been supported by NSF grant CCF-0622093 and NIH grant 1R21EB007472 to C.M. We thank W. Sherman for assistance in establishing the likely structural features of tensegrity triangles. We thank R. Sweet, M. Allaire, H. Robinson, A. Saxena and A. Héroux at the BNL-NSLS at beamlines X6A and X25 of the National Synchrotron Light Source. BNL-NSLS is supported principally from the Offices of Biological and Environmental Research and of Basic Energy Sciences of the US Department of Energy, and from the National Center for Research Resources of the National Institutes of Health. The use of the 19ID beamline at the Structural Biology Center/Advanced Photon Source is supported by the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357.

Author Contributions: J.Z. grew crystals, collected data, analysed data and wrote the paper; J.J.B. collected data, analysed data and wrote the paper; Y.C. grew crystals, collected data and analysed data; T.W. grew crystals, collected data, analysed data and wrote the paper; R.S. grew crystals, analysed data and wrote the paper; P.E.C. grew crystals and analysed data; S.L.G. collected data and analysed data; C.M. devised the motif, analysed data and wrote the paper; N.C.S. initiated the project, analysed data and wrote the paper.

Author information

Author notes

  1. Pamela E. Constantinou
    Present address: Present address: Department of Bioengineering, Rice University, 6100 Main Street, MS-142, Houston, Texas 77005, USA.,
  2. Jianping Zheng, Jens J. Birktoft and Yi Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, New York University, New York 10003, USA
    Jianping Zheng, Jens J. Birktoft, Tong Wang, Ruojie Sha, Pamela E. Constantinou & Nadrian C. Seeman
  2. Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA,
    Yi Chen & Chengde Mao
  3. Structural Biology Center, Argonne National Laboratory, Argonne, Illinois 60439, USA,
    Stephan L. Ginell

Authors

  1. Jianping Zheng
    You can also search for this author inPubMed Google Scholar
  2. Jens J. Birktoft
    You can also search for this author inPubMed Google Scholar
  3. Yi Chen
    You can also search for this author inPubMed Google Scholar
  4. Tong Wang
    You can also search for this author inPubMed Google Scholar
  5. Ruojie Sha
    You can also search for this author inPubMed Google Scholar
  6. Pamela E. Constantinou
    You can also search for this author inPubMed Google Scholar
  7. Stephan L. Ginell
    You can also search for this author inPubMed Google Scholar
  8. Chengde Mao
    You can also search for this author inPubMed Google Scholar
  9. Nadrian C. Seeman
    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence toChengde Mao or Nadrian C. Seeman.

Additional information

Atomic coordinates and experimental structure factors have been deposited within the Protein Data Bank and are accessible under the code 3GBI.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Table S1 and Supplementary References. (PDF 199 kb)

PowerPoint slides

Rights and permissions

About this article

Cite this article

Zheng, J., Birktoft, J., Chen, Y. et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal.Nature 461, 74–77 (2009). https://doi.org/10.1038/nature08274

Download citation

Editorial Summary

Designer DNA crystals

Creating a macroscopic object, such as a crystal, with the microscopic molecular structure desired is a challenge. One promising approach is the use of macromolecules with robust three-dimensional motifs and sticky ends so that, by attaching to one another, they can form a periodic arrangement that can be investigated by crystallographic techniques. Zheng et al. use DNA for this purpose, arranged in a structural motif called a tensegrity triangle, and can grow crystals of the order of 200 micrometres in size, in which the positions of the atoms can be determined with a precision of 4 Å. The highly specific interaction between complementary DNA strands makes it possible to realize the desired and designed structure for the unit cell of the crystal. The latter also exhibits periodic holes, which could potentially be used to host biomolecules in a three-dimensional periodic arrangement, making it possible to determine their structure even if they do not crystallize on their own.