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

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.