Designed Fibril-Forming Mini-Collagens Engineered to Exhibit up to Two Orders of Magnitude Differences in Rates of Matrix Metalloproteinase I Susceptibility.

The susceptibility to matrix metalloproteinases (MMPs) directly affects the functions and applications of collagen biomaterials. In this work, we demonstrated that this property can be manipulated in collagen-mimetic biomaterials created using designed peptides. We developed three fibril-forming mini-recombinant collagens (MRCs) using bacterial expression and designed genes that model a 108-residue section of human type III collagen surrounding the MMP-1 recognition site. Notably, the MRCs can form a native-like fibrillar structure representing the natural substrate of MMP-1. By altering the number of digestion sites or mutating the residues at the canonical scissile bond of MMP-1, the sensitivity to proteolysis of the MRCs varied by two orders of magnitude despite having homologous amino acid sequences and a similar fibrillar structure, and regardless of whether the peptides were in the triple helix conformation or as fibrils. These MRCs can be a versatile collagen alternative for regenerative medicine offering a regulated turnover rate catering to specific applications.