Design Strategies to Tune the Structural and Mechanical Properties of Synthetic Collagen Hydrogels

As an important component of biomaterials, collagen provides three-dimensional scaffolds and biological cues for cell adhesion and proliferation in tissue engineering. Recombinant collagen-like proteins, which were initially discovered in Streptococcus pyogenes and produced in heterologous hosts, have been chemically and genetically engineered for biomaterial applications. However, existing collagen-like proteins do not form gels, limiting their utility as biomaterials. Here, we present a series of rationally designed collagen-like proteins composed of a trimerization domain, triple-helical domains with various lengths and a pair of heterotrimeric coiled-coil sequences attached to the N- and C termini as adhesive ends. These designed proteins fold into triple helices and form self-supporting gels. As the triple-helical domains are lengthened, the gels become less stiff, pore sizes increase, and structural anisotropy decreases. Moreover, cell-culture assay confirms that the designed proteins are noncytotoxic. This study provides a design strategy for collagen-based biomaterials. The sequence variations reveal a relationship between the protein primary structure and material properties, where variations in the cross-linking density and association energies define the gelation of the protein network.

Automated summary

This study introduces a series of rationally designed collagen-like proteins that can form self-supporting gels and exhibit noncytotoxicity in cell-culture assays. As the triple-helical domains are lengthened, the gels become less stiff, pore sizes increase, and structural anisotropy decreases. Variations in the protein primary structure, such as cross-linking density and association energies, define the gelation of the protein network.