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:

Nanostructured films from hierarchical self-assembly of amyloidogenic proteins

Abstract

In nature, sophisticated functional materials are created through hierarchical self-assembly of simple nanoscale motifs1,2,3,4. In the laboratory, much progress has been made in the controlled assembly of molecules into one-5,6,7, two-6,8,9 and three-dimensional10 artificial nanostructures, but bridging from the nanoscale to the macroscale to create useful macroscopic materials remains a challenge. Here we show a scalable self-assembly approach to making free-standing films from amyloid protein fibrils. The films were well ordered and highly rigid, with a Young's modulus of up to 5–7 GPa, which is comparable to the highest values for proteinaceous materials found in nature. We show that the self-organizing protein scaffolds can align otherwise unstructured components (such as fluorophores) within the macroscopic films. Multiscale self-assembly that relies on highly specific biomolecular interactions is an attractive path for realizing new multifunctional materials built from the bottom up.

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

Access options

Buy this article

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

Figure 1: Fabrication of nanostructured films through multiscale hierarchical self-assembly.
Figure 2: Characterization of nanostructured protein films by X-ray diffraction studies.
Figure 3: Mechanical testing of nanostructured protein films in a three-point bending geometry.
Figure 4: Nanoscale alignment of fluorophores through self-organizing protein scaffolds.

Similar content being viewed by others

References

  1. Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).

    Article  CAS  Google Scholar 

  2. Buehler, M. J. & Ackbarow, T. Nanomechanical strength mechanisms of hierarchical biological materials and tissues. Comput. Methods Biomech. Biomed. Eng. 11, 595–607 (2008).

    Article  Google Scholar 

  3. Buehler, M. J. & Yung, Y. C. Deformation and failure of protein materials in physiologically extreme conditions and disease. Nature Mater. 8, 175–188 (2009).

    Article  CAS  Google Scholar 

  4. Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002).

    Article  CAS  Google Scholar 

  5. Kol, N. et al. Self-assembled peptide nanotubes are uniquely rigid bioinspired supramolecular structures. Nano Lett. 5, 1343–1346 (2005).

    Article  CAS  Google Scholar 

  6. Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 21, 1171–1178 (2003).

    Article  CAS  Google Scholar 

  7. Mao, C. et al. Virus-based toolkit for the directed synthesis of magnetic and semiconducting nanowires. Science 303, 213–217 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Zhang, S., Holmes, T., Lockshin, C. & Rich, A. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc. Natl Acad. Sci. USA 90, 3334–3338 (1993).

    Article  CAS  Google Scholar 

  10. 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 

  11. Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333–366 (2006).

    Article  CAS  Google Scholar 

  12. Kelly, J.W. Towards an understanding of amyloidogenesis. Nature Struct. Biol. 9, 323–325 (2002).

    Article  CAS  Google Scholar 

  13. Dobson, C. M. Protein misfolding, evolution and disease. Trends Biochem. Sci. 24, 329–332 (1999).

    Article  CAS  Google Scholar 

  14. Fändrich, M., Fletcher, M. A. & Dobson, C. M. Amyloid fibrils from myoglobin. Nature 410, 165–166 (2001).

    Article  Google Scholar 

  15. Fowler, D. M., Koulov, A. V., Balch, W. E. & Kelly, J. W. Functional amyloid—from bacteria to humans. Trends Biochem. Sci. 32, 217–224 (2007).

    Article  CAS  Google Scholar 

  16. Chapman, M. R. et al. Role of Escherichia coli curli operons in directing amyloid fiber formation. Science 295, 851–855 (2002).

    Article  CAS  Google Scholar 

  17. Maji, S. K. et al. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325, 328–332 (2009).

    Article  CAS  Google Scholar 

  18. Huang, Y., Duan, X., Wei, Q. & Lieber, C. M. Directed assembly of one-dimensional nanostructures into functional networks. Science 291, 630–633 (2001).

    Article  CAS  Google Scholar 

  19. Ikkala, O. & ten Brinke, G. Functional materials based on self-assembly of polymeric supramolecules. Science 295, 2407–2409 (2002).

    Article  CAS  Google Scholar 

  20. Knowles, T. P. et al. Role of intermolecular forces in defining material properties of protein nanofibrils. Science 318, 1900–1903 (2007).

    Article  CAS  Google Scholar 

  21. Reches, M. & Gazit, E. Controlled patterning of aligned self-assembled peptide nanotubes. Nature Nanotech. 1, 195–200 (2006).

    Article  CAS  Google Scholar 

  22. Gennadios, A. (ed.) Protein Based Films and Coatings (CRC Press, 2002).

    Book  Google Scholar 

  23. Sawaya, M. R. et al. Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature 447, 453–457 (2007).

    Article  CAS  Google Scholar 

  24. Jaroniec, C. P. et al. High resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc. Natl Acad. Sci. USA 101, 711–716 (2004).

    Article  CAS  Google Scholar 

  25. Donald, A. M., Windle, A. H. & Hanna, S. Liquid Crystalline Polymers 2nd edn (Cambridge Univ. Press, 2006).

    Book  Google Scholar 

  26. Corrigan, A. M., Müller, C. & Krebs, M. R. H. The formation of nematic liquid crystal phases by hen lysozyme amyloid fibrils. J. Am. Chem. Soc. 129, 14740–14741 (2006).

    Article  Google Scholar 

  27. Smith, J. F., Knowles, T. P. J., Dobson, C. M., Macphee, C. E. & Welland, M. E. Characterization of the nanoscale properties of individual amyloid fibrils. Proc. Natl Acad. Sci. USA 103, 15806–15811 (2006).

    Article  CAS  Google Scholar 

  28. Baughman, R. H., Zakhidov, A. A. & de Heer, W. A. Carbon nanotubes—the route toward applications. Science 297, 787–792 (2002).

    Article  CAS  Google Scholar 

  29. Krebs, M. R. H., Bromley, E. H. C. & Donald, A. M. The binding of thioflavin-T to amyloid fibrils: localisation and implications. J. Struct. Biol. 149, 30–37 (2005).

    Article  CAS  Google Scholar 

  30. Kosevich, A. M., Lifshitz, E. M., Landau, L. D. & Pitaevskii, L. P. Theory of Elasticity (Butterworth-Heinemann, 1986).

    Google Scholar 

Download references

Acknowledgements

The authors acknowledge support from Nokia Research Cambridge, the UK Engineering and Physical Sciences Research Council (EPSRC), the Interdisciplinary Research Council (IRC) in Nanotechnology, St John's College, Cambridge, and the Wellcome Trust. We thank C. Dobson, E. Eiser, M. Haddow and C. Meier for valuable discussions, and A. Rayment and I. Ganney for assistance with the mechanical measurements.

Author information

Authors and Affiliations

Authors

Contributions

T.P.J.K., T.W.O., A.K.B. and D.Y.C. performed the experiments. T.P.J.K., T.W.O., D.Y.C. and M.E.W. analysed the data. T.P.J.K., A.K.B. and M.E.W. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Mark E. Welland.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 325 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knowles, T., Oppenheim, T., Buell, A. et al. Nanostructured films from hierarchical self-assembly of amyloidogenic proteins. Nature Nanotech 5, 204–207 (2010). https://doi.org/10.1038/nnano.2010.26

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2010.26

This article is cited by

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