Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine

Bioengineering

JamesD. San Antonio¹  JosephP.R.O. Orgel²  Olena Jacenko³  Andrzej Fertala⁴ 

[1] Biocorda LLC, Media, PA 19063, USA;Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA;Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA;Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA;

关键词: type I collagen;    type III collagen;    interactome;    microfibril;    ligand binding;    extracellular matrix;   

DOI  :  10.3390/bioengineering8010003

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown