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Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and pot...

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Bibliographic Details
Published in:Nature communications 2017-03, Vol.8 (1), p.14913-14913, Article 14913
Main Authors: Zitnay, Jared L., Li, Yang, Qin, Zhao, San, Boi Hoa, Depalle, Baptiste, Reese, Shawn P., Buehler, Markus J., Yu, S. Michael, Weiss, Jeffrey A.
Format: Article
Language:English
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Summary:Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury. Collagen denaturation is thought to occur during tissue mechanical damage, but its role in damage initiation is still unclear. Here, the authors use a collagen hybridizing peptide to provide insights into the molecular mechanisms leading to collagen unfolding during tendon mechanical stretch.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms14913