Designed Fibril-Forming Mini-Collagens Engineered to Exhibit up to Two Orders of Magnitude Differences in Rates of Matrix Metalloproteinase I Susceptibility.
{"title":"Designed Fibril-Forming Mini-Collagens Engineered to Exhibit up to Two Orders of Magnitude Differences in Rates of Matrix Metalloproteinase I Susceptibility.","authors":"Jui Shivaji Chaugule, Yujia Xu","doi":"10.1021/acs.biomac.5c00026","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomacromolecules","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.biomac.5c00026","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine.
Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.