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 po...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/110088 https://orcid.org/0000-0002-4173-9659 |
| _version_ | 1811077301073346560 |
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| author | Zitnay, Jared L. Li, Yang San, Boi Hoa Reese, Shawn P. Yu, S. Michael Weiss, Jeffrey A. Qin, Zhao Depalle, Baptiste Pierre Jean Buehler, Markus J |
| author2 | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Zitnay, Jared L. Li, Yang San, Boi Hoa Reese, Shawn P. Yu, S. Michael Weiss, Jeffrey A. Qin, Zhao Depalle, Baptiste Pierre Jean Buehler, Markus J |
| author_sort | Zitnay, Jared L. |
| collection | MIT |
| description | 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 a-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. |
| first_indexed | 2024-09-23T10:40:47Z |
| format | Article |
| id | mit-1721.1/110088 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:40:47Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1100882022-09-30T22:14:25Z Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides Zitnay, Jared L. Li, Yang San, Boi Hoa Reese, Shawn P. Yu, S. Michael Weiss, Jeffrey A. Qin, Zhao Depalle, Baptiste Pierre Jean Buehler, Markus J Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Qin, Zhao Depalle, Baptiste Pierre Jean Buehler, Markus J 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 a-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. United States. Office of Naval Research. Presidential Early Career Award for Scientists and Engineers (N000141010562) United States. Air Force. Office of Scientific Research (FA95501110199) National Institutes of Health (U.S.) (TUFTS-5U01EB014976) National Institutes of Health (U.S.) (WUSTL- 5U01EB016422) Wellcome Trust (Grant WT097347MA) 2017-06-20T20:00:08Z 2017-06-20T20:00:08Z 2017-03 2015-11 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/110088 Zitnay, Jared L. et al. “Molecular Level Detection and Localization of Mechanical Damage in Collagen Enabled by Collagen Hybridizing Peptides.” Nature Communications 8 (2017): 14913. https://orcid.org/0000-0002-4173-9659 en_US http://dx.doi.org/10.1038/ncomms14913 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Zitnay, Jared L. Li, Yang San, Boi Hoa Reese, Shawn P. Yu, S. Michael Weiss, Jeffrey A. Qin, Zhao Depalle, Baptiste Pierre Jean Buehler, Markus J Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title | Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title_full | Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title_fullStr | Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title_full_unstemmed | Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title_short | Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| title_sort | molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides |
| url | http://hdl.handle.net/1721.1/110088 https://orcid.org/0000-0002-4173-9659 |
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