Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues

Zitnay, Jared L.; Jung, Gang Seob; Lin, Allen H.; Qin, Zhao; Li, Yang; Yu, S. Michael; Buehler, Markus J.; Weiss, Jeffrey A.

doi:10.1126/sciadv.aba2795

Title: Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues

Journal Article · Fri Aug 28 00:00:00 EDT 2020 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aba2795· OSTI ID:1659606

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Univ. of Utah, Salt Lake City, UT (United States). Dept. of Biomedical Engineering and Scientific Computing and Imaging (SCI) Inst.
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Civil and Environmental Engineering
Univ. of Utah, Salt Lake City, UT (United States). Dept. of Biomedical Engineering
Univ. of Utah, Salt Lake City, UT (United States). Dept. of Biomedical Engineering and Dept. of Pharmaceutics and Pharmaceutical Chemistry
Univ. of Utah, Salt Lake City, UT (United States). Dept. of Biomedical Engineering, Scientific Computing and Imaging (SCI) Inst., Dept. of Orthopaedics and School of Computing

Overuse injuries to dense collagenous tissues are common, but their etiology is poorly understood. The predominant hypothesis that micro-damage accumulation exceeds the rate of biological repair is missing a mechanistic explanation. Here, we used collagen hybridizing peptides to measure collagen molecular damage during tendon cyclic fatigue loading and computational simulations to identify potential explanations for our findings. Our results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate. Finite-element simulations demonstrated that biphasic fluid flow is a possible fascicle-level mechanism to explain the rate dependence of the number of cycles and time to failure. Molecular dynamics simulations demonstrated that triple-helical unfolding is rate dependent, revealing rate-dependent mechanisms at multiple length scales in the tissue. The accumulation of collagen molecular denaturation during cyclic loading provides a long-sought “micro-damage” mechanism for the development of overuse injuries.

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Research Organization:: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); US Department of the Navy, Office of Naval Research (ONR)

Grant/Contract Number:: F31EB023086; R01AR071358; U01EB014976; N00014-16-1-233

OSTI ID:: 1659606

Journal Information:: Science Advances, Vol. 6, Issue 35; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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