Skip to main content

Thank you for visiting 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.

Rational design and application of responsive α-helical peptide hydrogels


Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2,3,4. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril–fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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

Figure 1: hSAF design principles.
Figure 2: Gel strength and network formation by the hSAFs.
Figure 3: α-helical secondary structure and packing within the fibrils and gels.
Figure 4: Cell growth and differentiation on hSAF hydrogels.


  1. Hirst, A. R., Escuder, B., Miravet, J. F. & Smith, D. K. High-tech applications of self-assembling supramolecular nanostructured gel-phase materials: From regenerative medicine to electronic devices. Angew. Chem. Int. Ed. 47, 8002–8018 (2008).

    Article  CAS  Google Scholar 

  2. Woolfson, D. N. & Ryadnov, M. G. Peptide-based fibrous biomaterials: Some things old, new and borrowed. Curr. Opin. Chem. Biol. 10, 559–567 (2006).

    Article  CAS  Google Scholar 

  3. Kopeček, J. & Yang, J. Y. Peptide-directed self-assembly of hydrogels. Acta Biomater. 5, 805–816 (2009).

    Google Scholar 

  4. Ulijn, R. V. & Smith, A. M. Designing peptide based nanomaterials. Chem. Soc. Rev. 37, 664–675 (2008).

    CAS  Google Scholar 

  5. Hirst, A. R. & Smith, D. K. Two-component gel-phase materials—highly tunable self-assembling systems. Chem. Eur. J. 11, 5496–5508 (2005).

    Article  CAS  Google Scholar 

  6. Zhang, S. G., 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 

  7. Aggeli, A. et al. Responsive gels formed by the spontaneous self-assembly of peptides into polymeric beta-sheet tapes. Nature 386, 259–262 (1997).

    Article  CAS  Google Scholar 

  8. Pandya, M. J. et al. Sticky-end assembly of a designed peptide fiber provides insight into protein fibrillogenesis. Biochemistry 39, 8728–8734 (2000).

    Article  CAS  Google Scholar 

  9. Hartgerink, J. D., Beniash, E. & Stupp, S. I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).

    Article  CAS  Google Scholar 

  10. Schneider, J. P. et al. Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. J. Am. Chem. Soc. 124, 15030–15037 (2002).

    Article  CAS  Google Scholar 

  11. Paramonov, S., Gauba, V. & Hartgerink, J. Synthesis of collagen-like peptide polymers by native chemical ligation. Macromolecules 38, 7555–7561 (2005).

    Article  CAS  Google Scholar 

  12. Petka, W. A., Harden, J. L., McGrath, K. P., Wirtz, D. & Tirrell, D. A. Reversible hydrogels from self-assembling artificial proteins. Science 281, 389–392 (1998).

    Article  CAS  Google Scholar 

  13. Wang, C., Stewart, R. J. & Kopecek, J. Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature 397, 417–420 (1999).

    Article  CAS  Google Scholar 

  14. Potekhin, S. A. et al. De novo design of fibrils made of short alpha-helical coiled coil peptides. Chem. Biol. 8, 1025–1032 (2001).

    Article  CAS  Google Scholar 

  15. Zimenkov, Y., Conticello, V. P., Guo, L. & Thiyagarajan, P. Rational design of a nanoscale helical scaffold derived from self-assembly of a dimeric coiled coil motif. Tetrahedron 60, 7237–7246 (2004).

    Article  CAS  Google Scholar 

  16. Dong, H., Paramonov, S. E. & Hartgerink, J. D. Self-assembly of alpha-helical coiled coil nanofibers. J. Am. Chem. Soc. 130, 13691–13695 (2008).

    Article  CAS  Google Scholar 

  17. Gribbon, C. et al. MagicWand: A single, designed peptide that assembles to stable, ordered alpha-helical fibers. Biochemistry 47, 10365–10371 (2008).

    Article  CAS  Google Scholar 

  18. Ryadnov, M. G. & Woolfson, D. N. Engineering the morphology of a self-assembling protein fibre. Nature Mater. 2, 329–332 (2003).

    Article  CAS  Google Scholar 

  19. Papapostolou, D. et al. Engineering nanoscale order into a designed protein fiber. Proc. Natl Acad. Sci. USA 104, 10853–10858 (2007).

    Article  CAS  Google Scholar 

  20. Papapostolou, D., Bromley, E. H., Bano, C. & Woolfson, D. N. Electrostatic control of thickness and stiffness in a designed protein fiber. J. Am. Chem. Soc. 130, 5124–5130 (2008).

    Article  CAS  Google Scholar 

  21. Blake, C. & Serpell, L. Synchrotron X-ray studies suggest that the core of the transthyretin amyloid fibril is a continuous beta-sheet helix. Structure 4, 989–998 (1996).

    Article  CAS  Google Scholar 

  22. Perutz, M. F., Johnson, T., Suzuki, M. & Finch, J. T. Glutamine repeats as polar zippers—their possible role in inherited neurodegenerative diseases. Proc. Natl Acad. Sci. USA 91, 5355–5358 (1994).

    Article  CAS  Google Scholar 

  23. Sikorski, P. & Atkins, E. New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils. Biomacromolecules 6, 425–432 (2005).

    Article  CAS  Google Scholar 

  24. Hamid, R., Rotshteyn, Y., Rabadi, L., Parikh, R. & Bullock, P. Comparison of alamar blue and MTT assays for high through-put screening. Toxicol. Vitro 18, 703–710 (2004).

    Article  CAS  Google Scholar 

  25. Drubin, D. G., Feinstein, S. C., Shooter, E. M. & Kirschner, M. W. Nerve growth-factor induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors. J. Cell Biol. 101, 1799–1807 (1985).

    Article  CAS  Google Scholar 

  26. Debnath, J., Muthuswamy, S. K. & Brugge, J. S. Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30, 256–268 (2003).

    Article  CAS  Google Scholar 

  27. Todoroki, S., Morooka, H., Yamaguchi, M., Tsujita, T. & Sumikawa, K. Ropivacaine inhibits neurite outgrowth in PC-12 cells. Anesth. Analg. 99, 828–832 (2004).

    Article  CAS  Google Scholar 

  28. Pochan, D. J. et al. Thermally reversible hydrogels via intramolecular folding and consequent self-assembly of a de novo designed peptide. J. Am. Chem. Soc. 125, 11802–11803 (2003).

    Article  CAS  Google Scholar 

  29. Winn, M. D. An overview of the CCP4 project in protein crystallography: An example of a collaborative project. J. Synchrotron. Radiat. 10, 23–25 (2003).

    Article  CAS  Google Scholar 

  30. Makin, O. S., Sikorski, P. & Serpell, L. C. CLEARER: A new tool for the analysis of X-ray fibre diffraction patterns and diffraction simulation from atomic structural models. J. Appl. Crystallogr. 40, 966–972 (2007).

    Article  Google Scholar 

Download references


We are grateful to the BBSRC (IIP0307/003), the Royal College of Surgeons of England (for a Shapurji H. Modi Memorial ENT Research Fellowship to support E.S.A.) and Unilever for financial support. We thank D. Dawbarn for the gift of the PC12 cells and S. Furzeland and D. Atkins from Unilever for help with cryoEM.

Author information

Authors and Affiliations



E.F.B. and D.N.W. designed the peptides; E.F.B., E.S.A., D.J.A., M.F.B. and D.N.W. conceived and designed the experiments; E.F.B., E.S.A., A.C., M.K. and L.C.S. carried out the experiments; M.A.B. and A.M.D. co-supervised the cell biology and rheology, respectively; M.A.B. and M.F.B. co-supervised E.S.A. and E.F.B., respectively; D.N.W. coordinated, supervised and led the whole project; E.F.B. and D.N.W. wrote most of the paper.

Corresponding authors

Correspondence to Michael F. Butler or Derek N. Woolfson.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1159 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Banwell, E., Abelardo, E., Adams, D. et al. Rational design and application of responsive α-helical peptide hydrogels. Nature Mater 8, 596–600 (2009).

Download citation

  • Issue Date:

  • DOI:

This article is cited by


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