The influence of AGEs and enzymatic cross-links on the mechanical properties of collagen fibrils
Cross-links are considered to be a key component of collagen fibrils as they can change the fibrillar behavior in various ways. Advanced-Glycation Endproducts (AGEs), one particular type of cross-links, have been shown to accumulate and impair the mechanical properties of collageneous tissues, whereas enzymatic cross-links (ECLs) are known for stabilizing the structure of the fibril. However, the reasons for whether a given type of cross-link improves or impairs the material properties remain unknown. 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. 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 behaviour due to elevated AGEs content and could enable targeted measures regarding the reduction of specific collagen cross-linking levels.
Code (0)
등록된 구현이 없습니다.
Tasks
FrictionSimilar Papers 제목 키워드 기반
Learning graph representations of biochemical networks and its application to enzymatic link prediction
The complete characterization of enzymatic activities between molecules remains incomplete, hindering biological engineering and limiting biological discovery. We develop in this work a technique, Enzymatic Link Predicti…
Graph EmbeddingGraph LearningLink PredictionMineral and cross-linking in collagen fibrils: The mechanical behavior of bone tissue at the nano-scale
The mineralized collagen fibril is the main building block of hard tissues and it directly affects the macroscopic mechanics of biological tissues such as bone. The mechanical behavior of the fibril itself is determined …
Single-molecule stretching shows glycosylation sets tension in the hyaluronan-aggrecan bottlebrush
Large bottlebrush complexes formed from the polysaccharide hyaluronan (HA) and the proteoglycan aggrecan contribute to cartilage compression resistance and are necessary for healthy joint function. A variety of mechanica…
Reaction Engineering and Comparison of Electroenzymatic and Enzymatic ATP Regeneration Systems
Adenosine-5'-triphosphate (ATP) plays a crucial role in many biocatalytic reactions and its regeneration can influence the performance of a related enzymatic reaction significantly. Here, we established an electrochemica…
Modeling mechanical interactions in growing populations of rod-shaped bacteria
Advances in synthetic biology allow us to engineer bacterial collectives with pre-specified characteristics. However, the behavior of these collectives is difficult to understand, as cellular growth and division as well …