Rational design and application of responsive α-helical peptide hydrogels

Abstract

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.

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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.

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Acknowledgements

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.

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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.

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Banwell, E., Abelardo, E., Adams, D. et al. Rational design and application of responsive α-helical peptide hydrogels. Nature Mater 8, 596–600 (2009). https://doi.org/10.1038/nmat2479

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