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:

Tuning the erosion rate of artificial protein hydrogels through control of network topology

Abstract

Erosion behaviour governs the use of physical hydrogels in biomedical applications ranging from controlled release to cell encapsulation. Genetically engineered protein hydrogels offer unique means of controlling the erosion rate by engineering their amino acid sequences and network topology. Here, we show that the erosion rate of such materials can be tuned by harnessing selective molecular recognition, discrete aggregation number and orientational discrimination of coiled-coil protein domains. Hydrogels formed from a triblock artificial protein bearing dissimilar helical coiled-coil end domains (P and A) erode more than one hundredfold slower than hydrogels formed from those bearing the same end domains (either P or A). The reduced erosion rate is a consequence of the fact that looped chains are suppressed because P and A tend not to associate with each other. Thus, the erosion rate can be tuned over several orders of magnitude in artificial protein hydrogels, opening the door to diverse biomedical applications.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Schematic representations of triblock proteins and the amino acid sequences of major domains.
Figure 2: Structural and dynamic properties underlying the fast erosion of AC10A hydrogels.
Figure 3: Coiled-coil domains A and P do not associate with each other.
Figure 4: Dynamic moduli for AC10A (squares), PC10P (circles) and PC10A (triangles) hydrogels.
Figure 5: Erosion profiles.
Figure 6: The erosion profile of PC10A hydrogels (7% w/v) at 37 âˆ˜C in Dulbecco’s PBS (1×, pH 7.4).

Similar content being viewed by others

References

  1. 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  Google Scholar 

  2. Lee, K. Y. & Mooney, D. J. Hydrogels for tissue engineering. Chem. Rev. 101, 1869–1879 (2001).

    Article  Google Scholar 

  3. Anseth, K. S. et al. In situ forming degradable networks and their application in tissue engineering and drug delivery. J. Control. Release 78, 199–209 (2002).

    Article  Google Scholar 

  4. Yamaguchi, N. & Kiick, K. L. Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels. Biomacromolecules 6, 1921–1930 (2005).

    Article  Google Scholar 

  5. Rizzi, S. C. & Hubbell, J. A. Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part 1: Development and physicochernical characteristics. Biomacromolecules 6, 1226–1238 (2005).

    Article  Google Scholar 

  6. Kim, B. S., Hrkach, J. S. & Langer, R. Synthesis and characterization of novel degradable photocrosslinked poly(ether-anhydride) networks. J. Polym. Sci. A 38, 1277–1282 (2000).

    Article  Google Scholar 

  7. Kaczmarski, J. P. & Glass, J. E. Synthesis and solution properties of hydrophobically-modified ethoxylated urethanes with variable oxyethylene spacer lengths. Macromolecules 26, 5149–5156 (1993).

    Article  Google Scholar 

  8. Lundberg, D. J., Brown, R. G., Glass, J. E. & Eley, R. R. Synthesis, characterization, and solution rheology of model hydrophobically-modified, water-soluble ethoxylated urethanes. Langmuir 10, 3027–3034 (1994).

    Article  Google Scholar 

  9. Tam, K. C., Jenkins, R. D., Winnik, M. A. & Bassett, D. R. A structural model of hydrophobically modified urethane-ethoxylate (HEUR) associative polymers in shear flows. Macromolecules 31, 4149–4159 (1998).

    Article  Google Scholar 

  10. Li, J., Ni, X. P. & Leong, K. W. Injectable drug-delivery systems based on supramolecular hydrogels formed by poly(ethylene oxide) and alpha-cyclodextrin. J. Biomed. Mater. Res. A 65, 196–202 (2003).

    Article  Google Scholar 

  11. Anderson, B. C., Pandit, N. K. & Mallapragada, S. K. Understanding drug release from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) gels. J. Control. Release 70, 157–167 (2001).

    Article  Google Scholar 

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

    Article  Google Scholar 

  13. Pham, Q. T., Russel, W. B., Thibeault, J. C. & Lau, W. Micellar solutions of associative triblock copolymers: Entropic attraction and gas-liquid transition. Macromolecules 32, 2996–3005 (1999).

    Article  Google Scholar 

  14. Tae, G., Kornfield, J. A., Hubbell, J. A., Johannsmann, D. & Hogen-Esch, T. E. Hydrogels with controlled, surface erosion characteristics from self-assembly of fluoroalkyl-ended poly(ethylene glycol). Macromolecules 34, 6409–6419 (2001).

    Article  Google Scholar 

  15. Francois, J., Beaudoin, E. & Borisov, O. Association of hydrophobically end-capped poly(ethylene oxide). 2. Phase diagrams. Langmuir 19, 10011–10018 (2003).

    Article  Google Scholar 

  16. Shen, W. Structure, Dynamics, and Properties of Artificial Protein Hydrogels Assembled Through Coiled-Coil Domains. PhD Thesis, California Institute of Technology, Pasadena (2005).

  17. Kennedy, S. B. Biological Activity and Dynamic Structure in Artificial Protein Hydrogels. PhD Thesis, Univ. of Massachusetts Amherst, Amherst (2001).

  18. Malashkevich, V. N., Kammerer, R. A., Efimov, V. P., Schulthess, T. & Engel, J. The crystal structure of a five-stranded coiled coil in COMP: A prototype ion channel? Science 274, 761–765 (1996).

    Article  Google Scholar 

  19. Petka, W. A. Reversible Gelation of Genetically Engineered Macromolecules. PhD Thesis, Univ. of Massachusetts Amherst, Amherst (1997).

  20. Hodges, R. S. De novo design of alpha-helical proteins: Basic research to medical applications. Biochem. Cell Biol. 74, 133–154 (1996).

    Article  Google Scholar 

  21. Annable, T., Buscall, R., Ettelaie, R. & Whittlestone, D. The rheology of solutions of associating polymers—comparison of experimental behavior with transient network theory. J. Rheol. 37, 695–726 (1993).

    Article  Google Scholar 

  22. Harbury, P. B., Zhang, T., Kim, P. S. & Alber, T. A switch between 2-stranded, 3-stranded and 4-stranded coiled coils in Gcn4 Leucine-Zipper mutants. Science 262, 1401–1407 (1993).

    Article  Google Scholar 

  23. Kohn, W. D. & Hodges, R. S. De novo design of alpha-helical coiled coils and bundles: models for the development of protein-design principles. Trends Biotechnol. 16, 379–389 (1998).

    Article  Google Scholar 

  24. Litowski, J. R. & Hodges, R. S. Designing heterodimeric two-stranded alpha-helical coiled-coils—Effects of hydrophobicity and alpha-helical propensity on protein folding, stability, and specificity. J. Biol. Chem. 277, 37272–37279 (2002).

    Article  Google Scholar 

  25. Moll, J. R., Ruvinov, S. B., Pastan, I. & Vinson, C. Designed heterodimerizing leucine zippers with a range of pIs and stabilities up to 10(-15) M. Protein Sci. 10, 649–655 (2001).

    Article  Google Scholar 

  26. Wagschal, K., Tripet, B. & Hodges, R. S. De novo design of a model peptide sequence to examine the effects of single amino acid substitutions in the hydrophobic core on both stability and oligomerization state of coiled-coils. J. Mol. Biol. 285, 785–803 (1999).

    Article  Google Scholar 

  27. Yu, Y. B. Coiled-coils: stability, specificity, and drug delivery potential. Adv. Drug Delivery Rev. 54, 1113–1129 (2002).

    Article  Google Scholar 

  28. Huglin, M. B. Light Scattering from Polymer Solutions (Academic, London, New York, 1972).

    Google Scholar 

  29. Hellman, U., Wernstedt, C., Gonez, J. & Heldin, C. H. Improvement of an in-gel digestion procedure for the micropreparation of internal protein-fragments for amino-acid sequencing. Anal. Biochem. 224, 451–455 (1995).

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the NSF Center for the Science and Engineering of Materials for financial support.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wei Shen, Kechun Zhang, Julia A. Kornfield or David A. Tirrell.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary information (PDF 48 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, W., Zhang, K., Kornfield, J. et al. Tuning the erosion rate of artificial protein hydrogels through control of network topology. Nature Mater 5, 153–158 (2006). https://doi.org/10.1038/nmat1573

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat1573

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