Biomaterial of the Month

Date: August 15 - October 1, 2011

"Designer Collagens"

"Designer Collagens" are collagen-mimetic proteins originally derived from a group A Streptococcus protein, Scl2.28, initially discovered by Dr. Höök of Texas A&M Health Science Center and Dr. Lukomski of West Virginia University.1-2 Although the Scl2.28 protein contains the GXY repeats characteristic of collagen, it lacks hydroxyproline and does not require post-translational modification to attain a triple helical structure.3 These features enable facile recombinant expression in E. coli, circumventing concerns about the batch variability of native collagens as well as the high scale-up costs associated with solid-phase synthesis of collagen-derived peptides.1-2

The parent "Designer Collagen" (DC1) was derived from the Scl2.28 sequence and lacks the array of cell adhesion, cytokine binding, and enzyme-cleavage sites associated with native collagen.4-5 DC1 therefore serves as a biological "blank slate" that only displays the selected receptor-binding sequences or enzyme-degradation sites programmed by site-directed mutagenesis. To date, ECM Technologies, a start-up founded by Dr. Magnus Höök, has generated two "daughter" DCs, DC2 and DC3, which incorporate α1β1 and/or α2β1 integrin-binding motifs based on the collagen sequences GF/LOGER6-7 (O; hydroxyproline). Specifically, DC2 binds both α1β1 and α2β1 integrins, whereas DC3 binds only α1β1.8 These daughter proteins maintain the resistance to platelet aggregation associated with DC18 while supporting cell-selective binding and appropriate integrin-mediated signaling.

Until recently, the use of DCs was limited to coatings due to their inability to self-assemble into stable 3D structures. However, DCs have now been successfully incorporated into 3D biomaterial platforms by coupling these proteins with established polymer chemistry to generate biosynthetic hydrogels based on functionalized DC and poly(ethylene glycol) diacrylate.9 Scl2.28-derived proteins have also been incorporated within 3D scaffolds via freeze-drying followed by glutaraldehyde crosslinking and have been shown to be cytocompatible and non-immunogenic in SJL/J and Arc mice.10 Given their unique properties, DCs represent a tailorable protein platform with strong potential utility in both fundamental and translational biomaterials research.

 

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References

  1. Xu, Y.; Keene, D.; Bujnicki, J.; Höök, M.; Lukomski, S., Scl1 and Scl2 proteins form collagen-like triple helices. Biol Chem 2002, 277, (30), 27312-8.
  2. Han, R.; Zwiefka, A.; Caswell, C.; Xu, Y.; Keene, D.; Lukomska, E.; Zhao, Z.; Höök, M.; Lukomski, S., Assessment of collagen-like sequences derived from Scl1 and Scl2 proteins as a source of recombinant GXY polymers. Applied Microbiology and Biotechnology 2006, 72, (1), 109-115.
  3. Brown, F. R.; Hopfinger, A. J.; Blout, E. R., The collagen-like triple helix to random-chain transition: Experiment and theory. Journal of Molecular Biology 1972, 63, (1), 101-115.
  4. Humtsoe, J. O.; Kim, J. K.; Xu, Y.; Keene, D. R.; Hook, M.; Lukomski, S.; Wary, K. K., A collagen-like protein interacts with the a2b1 integrin and induces intracellular signaling. Journal of Biological Chemistry 2005, 280, (14), 13848-13857.
  5. Caswell, C. C.; Barczyk, M.; Keene, D. R.; Lukomska, E.; Gullberg, D. E.; Lukomski, S., Identification of the first prokaryotic collagen sequence motif that mediates binding to human collagen receptors, integrins a2b1 and a11b1. Journal of Biological Chemistry 2008, 283, (52), 36168-36175.
  6. Kim, J. K.; Xu, Y.; Xu, X.; Keene, D. R.; Gurusiddappa, S.; Liang, X.; Wary, K. K.; Hook, M., A novel binding site in collagen type III for integrins a1b1 and a2b1. Journal of Biological Chemistry 2005, 280, (37), 32512-32520.
  7. Xu, Y.; Gurusiddappa, S.; Rich, R. L.; Owens, R. T.; Keene, D. R.; Mayne, R.; Hook, A.; Hook, M., Multiple binding sites in collagen type I for the integrins a1b1 and a2b1. Journal of Biological Chemistry 2000, 275, (50), 38981-38989.
  8. Seo, N.; Russell, B. H.; Rivera, J. J.; Liang, X.; Xu, X.; Afshar-Kharghan, V.; Höök, M., An Engineered α1 Integrin-binding Collagenous Sequence. Journal of Biological Chemistry 2010, 285, (40), 31046-31054.
  9. Cosgriff-Hernandez, E.; Hahn, M. S.; Russell, B.; Wilems, T.; Munoz-Pinto, D.; Browning, M. B.; Rivera, J.; Höök, M., Bioactive hydrogels based on Designer Collagens. Acta Biomaterialia 2010, 6, (10), 3969-3977.
  10. Peng, Y. Y.; Yoshizumi, A.; Danon, S. J.; Glattauer, V.; Prokopenko, O.; Mirochnitchenko, O.; Yu, Z.; Inouye, M.; Werkmeister, J. A.; Brodsky, B.; Ramshaw, J. A. M., A Streptococcus pyogenes derived collagen-like protein as a non-cytotoxic and non-immunogenic cross-linkable biomaterial. Biomaterials 2010, 31, (10), 2755-2761.

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