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

## TL;DR

Scientists engineered mini-collagen biomaterials with adjustable sensitivity to a specific enzyme, which could improve regenerative medicine applications.

## Contribution

Designed mini-collagens with tunable susceptibility to matrix metalloproteinase I by modifying digestion sites.

## Key findings

- MRCs formed native-like fibrillar structures similar to natural collagen substrates.
- Modifying digestion sites or residues altered proteolysis sensitivity by up to two orders of magnitude.
- MRCs offer a versatile collagen alternative with controllable turnover rates for biomedical use.

## Abstract

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.