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

Jared L. Zitnay, Yang Li, Zhao Qin, Boi Hoa San, Baptiste Depalle, Shawn P. Reese, Markus J. Buehler, S. Michael Yu, Jeffrey A. Weiss

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number14913
JournalNature communications
Volume8
DOIs
StatePublished - Mar 22 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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  • Cite this

    Zitnay, J. L., Li, Y., Qin, Z., San, B. H., Depalle, B., Reese, S. P., Buehler, M. J., Yu, S. M., & Weiss, J. A. (2017). Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides. Nature communications, 8, [14913]. https://doi.org/10.1038/ncomms14913