The influence of AGEs and enzymatic cross-links on the mechanical properties of collagen fibrils.

Autor: Kamml J; Institute for Building Materials, ETH Zurich, Switzerland., Ke CY; Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA., Acevedo C; Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA., Kammer DS; Institute for Building Materials, ETH Zurich, Switzerland. Electronic address: dkammer@ethz.ch.
Jazyk: angličtina
Zdroj: Journal of the mechanical behavior of biomedical materials [J Mech Behav Biomed Mater] 2023 Jul; Vol. 143, pp. 105870. Date of Electronic Publication: 2023 Apr 28.
DOI: 10.1016/j.jmbbm.2023.105870
Abstrakt: Collagen, one of the main building blocks for various tissues, derives its mechanical properties directly from its structure of cross-linked tropocollagen molecules. The cross-links are considered to be a key component of collagen fibrils as they can change the fibrillar behavior in various ways. For instance, enzymatic cross-links (ECLs), one particular type of cross-links, are known for stabilizing the structure of the fibril and improving material properties, while cross-linking AGEs (Advanced-Glycation Endproducts) have been shown to accumulate and impair the mechanical properties of collageneous tissues. However, the reasons for whether and how a given type of cross-link improves or impairs the material properties remain unknown, and the exact relationship between the cross-link properties and density, and the fibrillar behavior is still not well understood. Here, we use coarse-grained steered molecular models to evaluate the effect of AGEs and ECLs cross-links content on the deformation and failure properties of collagen fibrils. Our simulations show that the collagen fibrils stiffen at high strain levels when the AGEs content exceeds a critical value. In addition, the strength of the fibril increases with AGEs accumulation. By analyzing the forces within the different types of cross-links (AGEs and ECLs) as well as their failure, we demonstrate that a change of deformation mechanism is at the origin of these observations. A high AGEs content reinforces force transfer through AGEs cross-links rather than through friction between sliding tropocollagen molecules, which leads to failure by breaking of bonds within the tropocollagen molecules. We show that this failure mechanism, which is associated with lower energy dissipation, results in more abrupt failure of the collagen fibril. Our results provide a direct and causal link between increased AGEs content, inhibited intra-fibrillar sliding, increased stiffness, and abrupt fibril fracture. Therefore, they explain the mechanical origin of bone brittleness as commonly observed in elderly and diabetic populations. Our findings contribute to a better understanding of the mechanisms underlying impaired tissue behavior due to elevated AGEs content and could enable targeted measures regarding the reduction of specific collagen cross-linking levels.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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