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Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains

Abstract

Stimuli-sensitive polymer hydrogels, which swell or shrink in response to changes in the environmental conditions, have been extensively investigated and used as ‘smart’ biomaterials and drug-delivery systems1, 2. Most of these responsive hydrogels are prepared from a limited number of synthetic polymers and their derivatives, such as copolymers of (meth)acrylic acid, acrylamide and N-isopropyl acrylamide3,4,5,6,7,8,9,10,11,12. Water-soluble synthetic polymers have also been crosslinked with molecules of biological origin, such as oligopeptides13 and oligodeoxyribonucleotides14, or with intact native proteins15. Very often there are several factors influencing the relationship between structure and properties in these systems, making it difficult to engineer hydrogels with specified responses to particular stimuli. Here we report a hybrid hydrogel system assembled from water-soluble synthetic polymers and a well-defined protein-folding motif, the coiled coil. These hydrogels undergo temperature-induced collapse owing to the cooperative conformational transition of the coiled-coil protein domain. This system shows that well-characterized water-soluble synthetic polymers can be combined with well-defined folding motifs of proteins in hydrogels with engineered volume-change properties16, 17.

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Figure 1: Structural representation of the hybrid hydrogel primary chains and the attachment of His-tagged coiled-coil proteins.
Figure 2: The coiled coils and characterization by circular dichroism.
Figure 3: Dynamic swelling and the temperature-induced volume transition of the hybrid hydrogels in PBS.

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References

  1. Langer, R. Drug delivery and targeting. Nature 392 (suppl.), 5–10 (1998).

    Google Scholar 

  2. Peppas, N. A. Hydrogels and drug delivery. Curr. Opin. Colloid Interface Sci. 2, 531–537 (1997).

    Article  CAS  Google Scholar 

  3. Kopeček, J., Vacík, J. & Lím, D. Permeability of membranes containing ionogenic group. J. Polym. Sci. A-1 9,, 2801–2815 (1971).

    Article  Google Scholar 

  4. Suzuki, A. & Tanaka, T. Phase transition in polymer gels induced by visible light. Nature 346, 345–347 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Kokufuta, E., Zhang, Y. Q. & Tanaka, T. Saccharide-sensitive phase transition of a lectin-loaded gel. Nature 351, 302–304 (1991).

    Article  ADS  Google Scholar 

  6. Kwon, I. C., Bae, Y. H. & Kim, S. W. Electrically erodible polymer gel for controlled release of drugs. Nature 354, 291–293 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Osada, Y., Okuzaki, H. & Hori, H. Apolymer gel with electrically driven motility. Nature 355, 242–244 (1992).

    Article  ADS  CAS  Google Scholar 

  8. Chen, G. & Hoffman, A. S. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373, 49–52 (1995).

    Article  ADS  CAS  Google Scholar 

  9. Yoshida, R. et al. Comb-type grafted hydrogels with rapid de-swelling response to temperature changes. Nature 374, 240–242 (1995).

    Article  ADS  CAS  Google Scholar 

  10. Holtz, J. H. & Asher, S. A. Polymerized colloidal crystal hydrogel films as intelligent chemical sensing materials. Nature 389, 829–832 (1997).

    Article  ADS  CAS  Google Scholar 

  11. Hu, Z., Chen, Y., Wang, C., Zheng, Y. & Li, Y. Polymer gels with engineered environmentally responsive surface patterns. Nature 393, 149–152 (1998).

    Article  ADS  CAS  Google Scholar 

  12. Kiser, P. F., Wilson, G. & Needham, D. Asynthetic mimic of the secretory granule for drug delivery. Nature 394, 459–462 (1998).

    Article  ADS  CAS  Google Scholar 

  13. Šubr, V., Duncan, R. & Kopeček, J. Release of macromolecules and daunomycin from hydrophilic gels containing enzymatically degradable bonds. J. Biomater. Sci. Polym. Edn 1, 261–278 (1990).

    Article  Google Scholar 

  14. Nagahara, S. & Matsuda, T. Hydrogel formation via hybridization of oligonucleotides derivatized in water-soluble vinyl polymers. Polym. Gels Networks 4, 111–127 (1996).

    Article  CAS  Google Scholar 

  15. Obaidat, A. A. & Park, K. Characterization of glucose dependent gel-sol phase transition of the polymeric glucose-concanavalin A hydrogel system. Pharm. Res. 13, 989–995 (1996).

    Article  CAS  Google Scholar 

  16. Wang, C., Stewart, R. J. & Kopeček, J. De novo design of hybrid hydrogels: water soluble polymers crosslinked by coiled-coil protein domains. Proc. Int. Symp. Controlled Release Bioact. Mater. 25, 54–55 (1998).

    CAS  Google Scholar 

  17. Wang, C., Stewart, R. J. & Kopeček, J. Tailor-made hybrid hydrogels: synthetic macromolecules crosslinked by coiled-coil protein domains. ACS Polym. Preprints 39, 194–195 (1998).

    CAS  Google Scholar 

  18. Lupas, A. Coiled coils: new structures and new functions. Trends Biochem. Sci. 21, 375–382 (1996).

    Article  CAS  Google Scholar 

  19. O'Shea, E. K., Rutkowski, R. & Kim, P. S. Mechanism of specificity in the Fos-Jun oncoprotein heterodimer. Cell 68, 699–708 (1992).

    Article  CAS  Google Scholar 

  20. Harbury, P. B., Zhang, T., Kim, P. S. & Alber, T. Aswitch between two-, three-, and four-stranded coiled coils in GCN4 leucine zipper mutants. Science 262, 1401–1407 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Su, J. Y., Hodges, R. S. & Kay, C. M. Effect of chain length on the formation and stability of synthetic α-helical coiled coils. Biochemistry 33, 15501–15510 (1994).

    Article  CAS  Google Scholar 

  22. Gonzalez, L. J, Plecs, J. J. & Alber, T. An engineered allosteric switch in leucine-zipper oligomerization. Nature Struct. Biol. 3, 510–515 (1996).

    Article  CAS  Google Scholar 

  23. Hochuli, H. Purification of recombinant proteins with metal chelate adsorbent. Genet. Eng. 12, 87–98 (1990).

    Article  CAS  Google Scholar 

  24. Ng, K., Pack, D. W., Sasaki, D. Y. & Arnold, F. H. Engineered protein-lipid interactions: targeting of histidine-tagged proteins to metal-chelating lipid monolayers. Langmuir 11, 4048–4055 (1995).

    Article  CAS  Google Scholar 

  25. Ho, C. H., Limberis, L., Caldwell, K. D. & Stewart, R. J. Ametal-chelating pluronic for immobilization of histidine-tagged proteins at interfaces: immobilization of firefly luciferase on polystyrene beads. Langmuir 14, 3889–3894 (1998).

    Article  CAS  Google Scholar 

  26. Yang, J. T., Laymon, R. A. & Goldstein, L. S. B. Athree-domain structure of kinesin heavy chain revelaed by DNA sequence and microtubule binding analyses. Cell 56, 879–889 (1989).

    Article  CAS  Google Scholar 

  27. Graddis, T. J., Myszka, D. G. & Chaiken, I. M. Controlled formation of model homo- and heterodimer coiled coil polypeptides. Biochemistry 32, 12664–12671 (1993).

    Article  CAS  Google Scholar 

  28. Hirokawa, N. et al. Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration. Cell 56, 867–878 (1989).

    Article  CAS  Google Scholar 

  29. 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  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the Center for Biopolymers at Interfaces (CBI) and the University of Utah Research Foundation.

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Correspondence to JindŘich KopeČek.

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Wang, C., Stewart, R. & KopeČek, J. Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature 397, 417–420 (1999). https://doi.org/10.1038/17092

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