Article | Published:

Programmable molecular recognition based on the geometry of DNA nanostructures

Nature Chemistry volume 3, pages 620627 (2011) | Download Citation

  • An Erratum to this article was published on 23 September 2011

This article has been updated

Abstract

From ligand–receptor binding to DNA hybridization, molecular recognition plays a central role in biology. Over the past several decades, chemists have successfully reproduced the exquisite specificity of biomolecular interactions. However, engineering multiple specific interactions in synthetic systems remains difficult. DNA retains its position as the best medium with which to create orthogonal, isoenergetic interactions, based on the complementarity of Watson–Crick binding. Here we show that DNA can be used to create diverse bonds using an entirely different principle: the geometric arrangement of blunt-end stacking interactions. We show that both binary codes and shape complementarity can serve as a basis for such stacking bonds, and explore their specificity, thermodynamics and binding rules. Orthogonal stacking bonds were used to connect five distinct DNA origami. This work, which demonstrates how a single attractive interaction can be developed to create diverse bonds, may guide strategies for molecular recognition in systems beyond DNA nanostructures.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 15 August 2011

    In the version of this Article previously published, in Fig. 2, the series of 1s and 0s on the images were incorrectly placed. Also, in the penultimate paragraph of the section 'Stacking of origami rectangles', the final sentence should have referred to Fig.1e,g. These errors have now been corrected in the HTML and PDF versions of the Article.

References

  1. 1.

    Molecular recognition – a universal molecular science? Cell. Mol. Life Sci. 47, 1093–1095 (1991).

  2. 2.

    , , & Design of 240,000 orthogonal 25mer DNA barcode probes. Proc. Natl Acad. Sci. USA 106, 2289–2294 (2009).

  3. 3.

    Nucleic-acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).

  4. 4.

    , , & Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).

  5. 5.

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

  6. 6.

    , , & Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

  7. 7.

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

  8. 8.

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

  9. 9.

    Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994).

  10. 10.

    , , & An information-bearing seed for nucleating algorithmic self-assembly. Proc. Natl Acad. Sci. USA 106, 6054–6059 (2009).

  11. 11.

    , , & Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).

  12. 12.

    , , , & A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).

  13. 13.

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

  14. 14.

    , , & A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

  15. 15.

    & Heteroaromatic modules for self-assembly using multiple hydrogen bonds. Struct. Bonding 96, 63–94 (2000).

  16. 16.

    & π–π interactions in self-assembly. J. Phys. Org. Chem. 10, 254–272 (1997).

  17. 17.

    , & Engineering discrete stacks of aromatic molecules. Chem. Soc. Rev. 38, 1714–1725 (2009).

  18. 18.

    , , & Lock and key colloids. Nature 464, 575–578 (2010).

  19. 19.

    & Directing colloidal self-assembly through roughness-controlled depletion attractions. Phys. Rev. Lett. 99, 268301 (2007).

  20. 20.

    , , & Self-assembly of mesoscale objects into ordered two-dimensional arrays. Science 276, 233–235 (1997).

  21. 21.

    Using lateral capillary forces to compute by self-assembly. Proc. Natl Acad. Sci. USA 97, 984–989 (2000).

  22. 22.

    The design of coiled-coil structures and assemblies. Adv. Protein Chem. 70, 79–112 (2005).

  23. 23.

    Hydrogen bonding, base stacking, and steric effects in DNA replication. Annu. Rev. Biophys. Biomol. Struct. 30, 1–22 (2001).

  24. 24.

    , & Stacked–unstacked equilibrium at the nick site of DNA. J. Mol. Biol. 342, 775–785 (2004).

  25. 25.

    , & Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res. 34, 564–574 (2006).

  26. 26.

    & The stability of helical polynucleotides: base contributions. J. Mol. Biol. 4, 500–517 (1962).

  27. 27.

    & Theory of the melting transition of synthetic polynucleotides: evaluation of the stacking free energy. J. Mol. Biol. 9, 1–9 (1964).

  28. 28.

    & The thermodynamics of DNA structural motifs. Ann. Rev. Biophys. Biomol. Struct. 33, 415–440 (2004).

  29. 29.

    et al. End-to-end stacking and liquid crystal condensation of 6 to 20 base pair DNA duplexes. Science 318, 1276–1279 (2007).

  30. 30.

    , , & Blunt-ended DNA stacking interactions in a 3-helix motif. Chem. Commun. 46, 4905–4907 (2010).

  31. 31.

    The origin of the genetic code. J. Mol. Biol. 38, 367–379 (1968).

  32. 32.

    Helical repeat of DNA in solution. Proc. Natl Acad. Sci. USA 76, 200–203 (1979).

  33. 33.

    , & Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009).

  34. 34.

    et al. Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 131, 15903–15908 (2009).

  35. 35.

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

  36. 36.

    et al. Polyelectrolyte-compression forces between spherical DNA brushes. Phys. Rev. Lett. 100, 118302 (2008).

  37. 37.

    , , , & Programmed-assembly system using DNA jigsaw pieces. Chem. Eur. J. 16, 5362–5368 (2010).

  38. 38.

    , & Studies of thermal stability of multivalent DNA hybridization in a nanostructured system. Biophys. J. 97, 563–571 (2009).

  39. 39.

    & Dynamic DNA nanotechnology using strand-displacement reactions. Nature Chem. 3, 103–113 (2011).

  40. 40.

    , , & Integrity of duplex structures without hydrogen bonding: DNA with pyrene paired at abasic sites. Nucleic Acids Res. 30, 5561–5569 (2002).

Download references

Acknowledgements

The authors gratefully acknowledge financial support for the Molecular Programming Project from the US National Science Foundation for Expeditions in Computing (No. 0832824, http://molecular-programming.org) and the Computer and Communication Foundations Emerging Models and Technologies grants No. 0829951 and No. 0622254, the Semiconductor Research Corporation Focus Center on Functional Engineered Nano Architectonics, the Microsoft Corporation and Mark Sims of Nanorex Corporation. S.W. thanks the Benjamin M. Rosen Family Foundation for a graduate fellowship. The authors thank the DNA and Natural Algorithms laboratory, and in particular L. Qian, N. Dabby, D. Doty, R. Schulman and J. Szablowski for comments.

Author information

Affiliations

  1. Department of Bioengineering, California Institute of Technology, Pasadena, California 91125, USA

    • Sungwook Woo
    •  & Paul W. K. Rothemund
  2. Department of Computer Science, California Institute of Technology, Pasadena, California 91125, USA

    • Paul W. K. Rothemund
  3. Department of Computation & Neural Systems, California Institute of Technology, Pasadena, California 91125, USA

    • Paul W. K. Rothemund

Authors

  1. Search for Sungwook Woo in:

  2. Search for Paul W. K. Rothemund in:

Contributions

S.W. and P.W.K.R. designed the experiments, analysed the data and co-wrote the paper. S.W. wrote the computer programs for designing bond types and performed binary code, shape code and thermodynamics experiments. P.W.K.R. performed cistrans isomerism experiments.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Sungwook Woo or Paul W. K. Rothemund.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Supplementary information

Zip files

  1. 1.

    Supplementary information

    Computer program codes for designing bond types (MATLAB files)

  2. 2.

    Supplementary information

    Installer for modified caDNAno program

  3. 3.

    Supplementary information

    caDNAno design files for shape systems (origami A,B,C, and D) and corner origami designs

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nchem.1070