Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides
Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms14913
Institutions: University of Utah, Massachusetts Institute of Technology
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Defense, University of Utah, Wellcome Trust, National Institutes of Health, Office of Naval Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, Air Force Office of Scientific Research
Awards: TAS::57 3600::TAS"TURNING WEAKNESS TO STRENGTH: MECHANOMUTABLE BIOINSPIRED MATERIALS,", G1890978812, IMAGING PROSTATE CANCER MICROENVIRONMENT BY COLLAGEN HYBIRDIZATION, Computational Framework for Multiscale Mechanics of Connective Tissues, G3469102124, Cross-scale interactions between mineral and collagen for tendon-bone attachment, G4043954581, G4119534169, G4410565212, PECASE: MERGER OF STRUCTURE AND MATERIAL: COMPARATIVE BOTTOM-UP ANALYSIS OF HIERARCHICAL PROTEIN MATERIALS, G4973927480, G5324093878, Models to Predict Protein Biomaterial Performance, Study and Application of Collagen Mimetic Peptide-Collagen Hybridization, Origins of Elasticity and Viscoelasticity in Ligaments, G5850682332, NCRR Confocal Proposal, G964493113, Collagen-Targeted Therapeutics of Cathepsin Inhibitors
OpenAlex ID: W2601951312