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:

Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly

Nature Chemistry volume 5, pages 868–875 (2013)Cite this article

Subjects

Abstract

Nature uses a combination of non-covalent interactions to create a hierarchy of complex systems from simple building blocks. One example is the selective association of the hydrophobic side chains that are a strong determinant of protein organization. Here, we report a parallel mode of assembly in DNA nanotechnology. Dendritic alkyl-DNA conjugates are hybridized to the edges of a DNA cube. When four amphiphiles are on one face, the hydrophobic residues of two neighbouring cubes engage in an intermolecular ‘handshake’, resulting in a dimer. When there are eight amphiphiles (four on the top and bottom cube faces, respectively), they engage in an intramolecular ‘handshake’ inside the cube. This forms the first example of a monodisperse micelle within a DNA nanostructure that encapsulates small molecules and releases them by DNA recognition. Creating a three-dimensional pattern of hydrophobic patches, like side chains in proteins, can result in specific, directed association of hydrophobic domains with orthogonal interactions to DNA base-pairing.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Different modes of D-DNA assembly.
Figure 2: Structure, characterization and self-assembly of D-DNA.
Figure 3: Assembly and decoration of a DNA cube.
Figure 4: Intermolecular hydrophobic association upon decoration of cube with four D2.
Figure 5: Assembly of core–shell structures.
Figure 6: Encapsulation and release in cube-core structures.

Similar content being viewed by others

References

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

    Article  Google Scholar 

  2. Lin, C., Liu, Y. & Yan, H. Designer DNA nanoarchitectures. Biochemistry 48, 1663–1674 (2009).

    Article  CAS  Google Scholar 

  3. Deng, Z., Lee, S. H. & Mao, C. DNA as nanoscale building blocks. J. Nanosci. Nanotechnol. 5, 1954–1963 (2005).

    Article  CAS  Google Scholar 

  4. Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Woo, S. & Rothemund, P. W. K. Programmable molecular recognition based on the geometry of DNA nanostructures. Nature Chem. 3, 620–627 (2011).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Han, D. et al. DNA origami with complex curvatures in three-dimensional space. Science 332, 342–346 (2011).

    Article  CAS  Google Scholar 

  9. Andersen, E. S. et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73–76 (2009).

    Article  CAS  Google Scholar 

  10. Schulman, R., Yurke, B. & Winfree, E. Robust self-replication of combinatorial information via crystal growth and scission. Proc. Natl Acad. Sci. USA 109, 6405–6410 (2012).

    Article  CAS  Google Scholar 

  11. Rajendran, A., Endo, M., Katsuda, Y., Hidaka, K. & Sugiyama, H. Programmed two-dimensional self-assembly of multiple DNA origami jigsaw pieces. ACS Nano 5, 665–671 (2010).

    Article  Google Scholar 

  12. 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 

  13. Yang, H. et al. Metal–nucleic acid cages. Nature Chem. 1, 390–396 (2009).

    Article  CAS  Google Scholar 

  14. Wang, W., Wan, W., Zhou, H.-H., Niu, S. & Li, A. D. Q. Alternating DNA and π-conjugated sequences. Thermophilic foldable polymers. J. Am. Chem. Soc. 125, 5248–5249 (2003).

    Article  CAS  Google Scholar 

  15. Carneiro, K. M. M. et al. Stimuli-responsive organization of block copolymers on DNA nanotubes. Chem. Sci. 3, 1980–1986 (2012).

    Article  CAS  Google Scholar 

  16. Milnes, P. J. et al. Sequence-specific synthesis of macromolecules using DNA-templated chemistry. Chem. Commun. 48, 5614–5616 (2012).

    Article  CAS  Google Scholar 

  17. Kwak, M. & Herrmann, A. Nucleic acid amphiphiles: synthesis and self-assembled nanostructures. Chem. Soc. Rev. 40, 5745–5755 (2011).

    Article  CAS  Google Scholar 

  18. Neelakandan, P. P. et al. Hydrophobic self-assembly of a perylenediimide-linked DNA dumbbell into supramolecular polymers. J. Am. Chem. Soc. 132, 15808–15813 (2010).

    Article  CAS  Google Scholar 

  19. Eryazici, I., Yildirim, I., Schatz, G. C. & Nguyen, S. T. Enhancing the melting properties of small molecule–DNA hybrids through designed hydrophobic interactions: an experimental–computational study. J. Am. Chem. Soc. 134, 7450–7458 (2012).

    Article  CAS  Google Scholar 

  20. Patwa, A., Gissot, A., Bestel, I. & Barthélémy, P. Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications. Chem. Soc. Rev. 40, 5844–5854 (2011).

    Article  CAS  Google Scholar 

  21. Chan, Y. H., Lenz, P. & Boxer, S. G. Kinetics of DNA-mediated docking reactions between vesicles tethered to supported lipid bilayers. Proc. Natl Acad. Sci. USA 104, 18913–18918 (2007).

    Article  CAS  Google Scholar 

  22. Woller, J. G., Börjesson, K., Svedhem, S. & Albinsson, B. Reversible hybridization of DNA anchored to a lipid membrane via porphyrin. Langmuir: ACS J. Surf. Colloids 28, 1944–1953 (2012).

    Article  CAS  Google Scholar 

  23. Benkoskr, J. J. & Höök, F. Lateral mobility of tethered vesicle–DNA assemblies. J. Phys. Chem. B 109, 9773–9779 (2005).

    Article  Google Scholar 

  24. Albinsson, B., Hannestad, J. K. & Börjesson, K. Functionalized DNA nanostructures for light harvesting and charge separation. Coord. Chem. Rev. 256, 2399–2413 (2012).

    Article  CAS  Google Scholar 

  25. Langecker, M. et al. Synthetic lipid membrane channels formed by designed DNA nanostructures. Science 338, 932–936 (2012).

    Article  CAS  Google Scholar 

  26. Raouane, M., Desmaële, D., Urbinati, G., Massaad-Massade, L. & Couvreur, P. Lipid conjugated oligonucleotides: a useful strategy for delivery. Bioconj. Chem. 23, 1091–1104 (2012).

    Article  CAS  Google Scholar 

  27. Thompson, M. P., Chien, M.-P., Ku, T.-H., Rush, A. M. & Gianneschi, N. C. Smart lipids for programmable nanomaterials. Nano Lett. 10, 2690–2693 (2010).

    Article  CAS  Google Scholar 

  28. Kurz, A. et al. Lipid-anchored oligonucleotides for stable double-helix formation in distinct membrane domains. Angew. Chem. Int. Ed. 45, 4440–4444 (2006).

    Article  CAS  Google Scholar 

  29. O'Shea, E. K., Klemm, J. D., Kim, P. S. & Alber, T. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254, 539–544 (1991).

    Article  CAS  Google Scholar 

  30. Koga, N. et al. Principles for designing ideal protein structures. Nature 491, 222–227 (2012).

    Article  CAS  Google Scholar 

  31. Boyle, A. L. et al. Squaring the circle in peptide assembly: from fibers to discrete nanostructures by de novo design. J. Am. Chem. Soc. 134, 15457–15467 (2012).

    Article  CAS  Google Scholar 

  32. Schnitzler, T. & Herrmann, A. DNA block copolymers: functional materials for nanoscience and biomedicine. Acc. Chem. Res. 45, 1419–1430 (2012).

    Article  CAS  Google Scholar 

  33. Wu, Y., Sefah, K., Liu, H., Wang, R. & Tan, W. DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells. Proc. Natl Acad. Sci. USA 107, 5–10 (2010).

    Article  CAS  Google Scholar 

  34. Wang, L. et al. Reversibly controlled morphology transformation of an amphiphilic DNA–dendron hybrid. Chem. Commun. 48, 3715–3717 (2012).

    Article  CAS  Google Scholar 

  35. Ponnuswamy, N., Cougnon, F. B. L., Clough, J. M., Pantoş, G. D. & Sanders, J. K. M. Discovery of an organic trefoil knot. Science 338, 783–785 (2012).

    Article  CAS  Google Scholar 

  36. Wenz, G., Han, B.-H. & Müller, A. Cyclodextrin rotaxanes and polyrotaxanes. Chem. Rev. 106, 782–817 (2006).

    Article  CAS  Google Scholar 

  37. Kilah, N. L. et al. Enhancement of anion recognition exhibited by a halogen-bonding rotaxane host system. J. Am. Chem. Soc. 132, 11893–11895 (2010).

    Article  CAS  Google Scholar 

  38. Liu, H. et al. DNA-based micelles: synthesis, micellar properties and size-dependent cell permeability. Chem. Eur. J. 16, 3791–3797 (2010).

    Article  CAS  Google Scholar 

  39. Greenspan, P., Mayer, E. P. & Fowler, S. D. Nile red: a selective fluorescent stain for intracellular lipid droplets. J. Cell Biol. 100, 965–973 (1985).

    Article  CAS  Google Scholar 

  40. Greenspan, P. & Fowler, S. D. Spectrofluorometric studies of the lipid probe, Nile red. J. Lipid Res. 26, 781–789 (1985).

    CAS  PubMed  Google Scholar 

  41. McLaughlin, C. K. et al. Three-dimensional organization of block copolymers on ‘DNA- minimal' scaffolds. J. Am. Chem. Soc. 134, 4280–4286 (2012).

    Article  CAS  Google Scholar 

  42. Borjesson, K., Lundberg, E. P., Woller, J. G., Norden, B. & Albinsson, B. Soft-surface DNA nanotechnology: DNA constructs anchored and aligned to lipid membrane. Angew. Chem. Int. Ed. 50, 8312–8315 (2011).

    Article  Google Scholar 

  43. Ding, K., Alemdaroglu, F. E., Börsch, M., Berger, R. & Herrmann, A. Engineering the structural properties of DNA block copolymer micelles by molecular recognition. Angew. Chem. Int. Ed. 46, 1172–1175 (2007).

    Article  CAS  Google Scholar 

  44. Chien, M.-P., Rush, A. M., Thompson, M. P. & Gianneschi, N. C. Programmable shape-shifting micelles. Angew. Chem. Int. Ed. 49, 5076–5080 (2010).

    Article  CAS  Google Scholar 

  45. Lo, P. K. et al. Loading and selective release of cargo in DNA nanotubes with longitudinal variation. Nature Chem. 2, 319–328 (2010).

    Article  CAS  Google Scholar 

  46. Erben, C. M., Goodman, R. P. & Turberfield, A. J. Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Ed. 45, 7414–7417 (2006).

    Article  CAS  Google Scholar 

  47. Jiang, Q. et al. DNA origami as a carrier for circumvention of drug resistance. J. Am. Chem. Soc. 134, 13396–13403 (2012).

    Article  CAS  Google Scholar 

  48. Lim, Y.-b., Lee, E. & Lee, M. Controlled bioactive nanostructures from self-assembly of peptide building blocks. Angew. Chem. Int. Ed. 46, 9011–9014 (2007).

    Article  CAS  Google Scholar 

  49. Cao, P. & Bae, Y. Polymer nanoparticulate drug delivery and combination cancer therapy. Future Oncol. 8, 1471–1480 (2012).

    Article  CAS  Google Scholar 

  50. Carneiro, K. M. M., Aldaye, F. A. & Sleiman, H. F. Long-range assembly of DNA into nanofibers and highly ordered networks using a block copolymer approach. J. Am. Chem. Soc. 132, 679–685 (2009).

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Foundation for Innovation (CFI), the Centre for Self-Assembled Chemical Structures (CSACS) and the Canadian Institute for Advanced Research (CIFAR) for financial support. T.G.W.E thanks Canadian Institutes of Health Research (CIHR) for a Drug Development Training Program (DDTP) scholarship. C.J.S thanks NSERC for a Banting Postdoctoral Fellowship. H.F.S. is a Cottrell Scholar of the Research Corporation.

Author information

Authors and Affiliations

  1. Department of Chemistry and Centre for Self-assembled Chemical Structures, McGill University, Montreal, QC H3A2K6, 801 Sherbrooke Street West, Canada

    Thomas G. W. Edwardson, Karina M. M. Carneiro, Christopher K. McLaughlin, Christopher J. Serpell & Hanadi F. Sleiman

Authors
  1. Thomas G. W. Edwardson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karina M. M. Carneiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher K. McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher J. Serpell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanadi F. Sleiman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.F.S., T.G.W.E. and K.M.M.C. designed the project. T.G.W.E. primarily contributed to the production of experimental results. T.G.W.E. and K.M.M.C. developed the synthesis of the D-DNA. T.G.W.E. and C.K.M. designed and synthesized the sequences for the DNA scaffold and additional unmodified DNA. All authors discussed the results, commented on the manuscript and have agreed to all the content of the manuscript.

Corresponding author

Correspondence to Hanadi F. Sleiman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 2766 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edwardson, T., Carneiro, K., McLaughlin, C. et al. Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly. Nature Chem 5, 868–875 (2013). https://doi.org/10.1038/nchem.1745

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.1745

This article is cited by

Search

Advanced 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