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.

  • Letter
  • Published:

Amyloid fibrils nucleated and organized by DNA origami constructions

Nature Nanotechnology volume 9, pages 537–541 (2014)Cite this article

Subjects

Abstract

Amyloid fibrils are ordered, insoluble protein aggregates that are associated with neurodegenerative conditions such as Alzheimer's disease1. The fibrils have a common rod-like core structure, formed from an elongated stack of β-strands, and have a rigidity similar to that of silk (Young's modulus of 0.2–14 GPa)2. They also exhibit high thermal and chemical stability3 and can be assembled in vitro from short synthetic non-disease-related peptides4,5. As a result, they are of significant interest in the development of self-assembled materials for bionanotechnology applications6. Synthetic DNA molecules have previously been used to form intricate structures and organize other materials such as metal nanoparticles7,8 and could in principle be used to nucleate and organize amyloid fibrils. Here, we show that DNA origami nanotubes can sheathe amyloid fibrils formed within them. The fibrils are built by modifying the synthetic peptide fragment corresponding to residues 105–115 of the amyloidogenic protein transthyretin9 and a DNA origami10 construct is used to form 20-helix DNA nanotubes with sufficient space for the fibrils inside. Once formed, the fibril-filled nanotubes can be organized onto predefined two-dimensional platforms via DNA–DNA hybridization interactions.

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: Process of organizing amyloid fibrils using DNA origami.
Figure 2: Components of the system.
Figure 3: Amyloid fibrils organized onto DNA origami platforms.

Similar content being viewed by others

References

  1. Tan, S. Y. & Pepys, M. B. Amyloidosis. Histopathology 25, 403–414 (1994).

    Article  CAS  Google Scholar 

  2. Knowles, T. P. J. & Buehler, M. J. Nanomechanics of functional and pathological amyloid materials. Nature Nanotech. 6, 469–479 (2011).

    Article  CAS  Google Scholar 

  3. Mesquida, P., Riener, C. K., MacPhee, C. E. & McKendry, R. A. Morphology and mechanical stability of amyloid-like peptide fibrils. J. Mater. Sci. Mater. Med. 18, 1325–1331 (2007).

    Article  CAS  Google Scholar 

  4. Guijarro, J. I., Sunde, M., Jones, J. A., Campbell, I. D. & Dobson, C. M. Amyloid fibril formation by an SH3 domain. Proc. Natl Acad. Sci. USA 95, 4224–4228 (1998).

    Article  CAS  Google Scholar 

  5. Chiti, F. et al. Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc. Natl Acad. Sci. USA 96, 3590–3594 (1999).

    Article  CAS  Google Scholar 

  6. Gras, S. L. Amyloid fibrils: From disease to design. New biomaterial applications for self-assembling cross-beta fibrils. Aust. J. Chem. 60, 333–342 (2007).

    Article  CAS  Google Scholar 

  7. Seeman, N. C. Nucleic acid junctions and lattice. J. Theor. Biol. 99, 237–247 (1982).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Gustavsson, A., Engstrom, U. & Westermark, P. Normal transthyretin and synthetic transthyretin fragments form amyloid-like fibrils in vitro. Biochem. Biophys. Res. Commun. 175, 1159–1164 (1991).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Sherman, W. B. & Seeman, N. C. Design of minimally strained nucleic acid nanotubes. Biophys. J. 90, 4546–4547 (2006).

    Article  CAS  Google Scholar 

  12. Fitzpatrick, A. W. P. et al. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proc. Natl Acad. Sci. USA 110, 5468–5473 (2013).

    Article  CAS  Google Scholar 

  13. Jaroniec, C. P., MacPhee, C. E., Astrof, N. S., Dobson, C. M. & Griffin, R. G. Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril. Proc. Natl Acad. Sci. USA 99, 16748–16753 (2002).

    Article  CAS  Google Scholar 

  14. Caporini, M. A. et al. Accurate determination of interstrand distances and alignment in amyloid fibrils by magic angle spinning NMR. J. Phys. Chem. B 114, 13555–13561 (2010).

    Article  CAS  Google Scholar 

  15. Bongiovanni, M. N., Puri, D., Goldie, K. N. & Gras, S. L. Noncore residues influence the kinetics of functional TTR105–115-based amyloid fibril assembly. J. Mol. Biol. 421, 256–269 (2012).

    Article  CAS  Google Scholar 

  16. Bongiovanni, M. N., Caruso, F. & Gras, S. L. Lysine functionalised amyloid fibrils: the design and assembly of a TTR1-based peptide. Soft Matter 9, 3315–3330 (2013).

    Article  CAS  Google Scholar 

  17. Gras, S. L. et al. Functionalized amyloid fibrils for roles in cell adhesion. Biomaterials 29, 1553–1562 (2008).

    Article  CAS  Google Scholar 

  18. MacPhee, C. E. & Dobson, C. M. Formation of mixed fibrils demonstrates the generic nature and potential utility of amyloid nanostructures. J. Am. Chem. Soc. 122, 12707–12713 (2000).

    Article  CAS  Google Scholar 

  19. Glen Report 15.1, A novel route to activated carboxylate modified oligonucleotides. Available from http://www.glenresearch.com//glenreports/gr15-15.html.

  20. Wright, C. F., Teichmann, S. A., Clark, J. & Dobson, C. M. The importance of sequence diversity to the aggregation and evolution of proteins. Nature 438, 878–881 (2005).

    Article  CAS  Google Scholar 

  21. Bongiovanni, M. N., Puri, D., Goldie, K. N. & Gras, S. L. Noncore residues influence the kinetics of functional TTR105–115-based amyloid fibril assembly. J. Mol. Biol. 421, 256–269 (2012).

    Article  CAS  Google Scholar 

  22. Mesquida, P., Ammann, D. L., MacPhee, C. E. & McKendry, R. A. Microarrays of peptide fibrils created by electrostatically controlled deposition. Adv. Mater. 17, 893–897 (2005).

    Article  CAS  Google Scholar 

  23. Mesquida, P., Blanco, E. M. & McKendry, R. A. Patterning amyloid peptide fibrils by AFM charge writing. Langmuir 22, 9089–9091 (2006).

    Article  CAS  Google Scholar 

  24. Yang, X. et al. Two-dimensional graphene nanoribbons. J. Am. Chem. Soc. 130, 4216–4217 (2008).

    Article  CAS  Google Scholar 

  25. Han, T. H. et al. Peptide/graphene hybrid assembly into core/shell nanowires. Adv. Mater. 22, 2060–2064 (2010).

    Article  CAS  Google Scholar 

  26. Li, C., Adamcik, J. & Raffaele Mezzenga, R. Biodegradable nanocomposites of amyloid fibrils and graphene with shape-memory and enzyme-sensing properties. Nature Nanotech. 7, 421–427 (2012).

    Article  CAS  Google Scholar 

  27. 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 

  28. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 85, 2149–2154 (1963).

    Article  CAS  Google Scholar 

  29. Gras, S. L. et al. Functionalized amyloid fibrils for roles in cell adhesion. Biomaterials 29, 1553–1562 (2008).

    Article  CAS  Google Scholar 

  30. McPhillips, T. M. et al. Blu-ice and the distributed control system: software for data acquisition and instrument control at macromolecular crystallography beamlines. J. Synchrotron Radiat. 9, 401–406 (2002).

    Article  CAS  Google Scholar 

  31. http://www.nanoengineer-1.com/content/

Download references

Acknowledgements

This research was supported by the following grants to N.C.S.: grant no. GM-29554 from the National Institute of General Medical Sciences, grants nos CMMI-1120890 and CCF-1117210 from the National Science Foundation, MURI W911NF-11-1-0024 from the Army Research Office, and grants nos N000141110729 and N000140911118 from the Office of Naval Research. M.N.B. was supported by an Australian Nanotechnology Network Overseas Travel Fellowship, a Melbourne Abroad Travelling Scholarship and the Bio21 Institute. S.L.G. and M.N.B. were supported by the Particulate Fluids Processing Centre and S.L.G. by the ARC Dairy Innovation Hub. Part of this research was carried out at the Macromolecular Crystallography beamline at the Australian Synchrotron, Victoria, Australia. Research was carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the US Department of Energy, Office of Basic Energy Sciences (contract no. DE-AC02-98CH10886).

Author information

Authors and Affiliations

  1. Department of Chemistry, New York University, New York, 10003, New York, USA

    Anuttara Udomprasert, Ruojie Sha, Tong Wang, Paramjit S. Arora, James W. Canary & Nadrian C. Seeman

  2. Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, 3010, Victoria, Australia

    Marie N. Bongiovanni & Sally L. Gras

  3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, 3010, Victoria, Australia

    Marie N. Bongiovanni & Sally L. Gras

  4. Bard High School Early College—Queens, 30-20 Thomson Avenue, Queens, 11101, New York, USA

    William B. Sherman

Authors
  1. Anuttara Udomprasert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie N. Bongiovanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruojie Sha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William B. Sherman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paramjit S. Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James W. Canary
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sally L. Gras
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nadrian C. Seeman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.U., M.N.B., R.J.S., W.B.S. and T.W. carried out experiments and wrote the manuscript. P.S.A. co-designed the peptide conjugation experiments and wrote the manuscript. J.W.C. wrote the manuscript. S.L.G. conceived and directed the project, and wrote the manuscript. N.C.S. conceived and directed the project and wrote the manuscript.

Corresponding authors

Correspondence to Sally L. Gras or Nadrian C. Seeman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Information (PDF 4326 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Udomprasert, A., Bongiovanni, M., Sha, R. et al. Amyloid fibrils nucleated and organized by DNA origami constructions. Nature Nanotech 9, 537–541 (2014). https://doi.org/10.1038/nnano.2014.102

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2014.102

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