Document Type
Article
Publication Date
1-1-2021
Abstract
Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, and brittle bone disease. To elucidate the type I collagen structure-function relationship, we constructed a type I collagen fibril interactome, including its functional sites and disease-associated mutations. When projected onto an X-ray diffraction model of the native collagen microfibril, data revealed a matrix interaction domain that assumes structural roles including collagen assembly, crosslinking, proteoglycan (PG) binding, and mineralization, and the cell interaction domain supporting dynamic aspects of collagen biology such as hemostasis, tissue remodeling, and cell adhesion. Our type III collagen interactome corroborates this model. We propose that in quiescent tissues, the fibril projects a structural face; however, tissue injury releases blood into the collagenous stroma, triggering exposure of the fibrils' cell and ligand binding sites crucial for tissue remodeling and regeneration. Applications of our research include discovery of anti-fibrotic antibodies and elucidating their interactions with collagen, and using insights from our angiogenesis studies and collagen structure-function model to inform the design of super-angiogenic collagens and collagen mimetics.
Recommended Citation
San Antonio, James D; Jacenko, Olena; Fertala, Andrzej; and Orgel, Joseph P R O, "Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine." (2021). Department of Orthopaedic Surgery Faculty Papers. Paper 145.
https://jdc.jefferson.edu/orthofp/145
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
33383610
Comments
This article has been peer reviewed. It was published in: Bioengineering.
Volume 8, Issue 1, January 2021, Article number 3, Pages 1-23.
The published version is available at https://doi.org/10.3390/bioengineering8010003
Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).