AGEs和酶交联对胶原纤维力学性能的影响
The influence of AGEs and enzymatic cross-links on the mechanical properties of collagen fibrils
摘要：
交联被认为是胶原原纤维的关键组分，因为它们可以以各种方式改变原纤维行为。高级糖基化终产物（AGEs），一种特殊类型的交联，已被证明积累并损害胶原组织的机械性质，而酶交联（ECL）已知用于稳定原纤维的结构。然而，对于给定类型的交联是否改善或损害材料性质的原因仍然未知。在这里，我们使用粗粒度的转向分子模型来评估AGEs和ECL交联含量对胶原纤维的变形和失效特性的影响。我们的模拟表明，胶原纤维在高应变水平时，AGEs含量超过一个临界值。此外，纤维的强度随着AGEs的积累而增加。通过分析不同类型的交联（AGEs和ECL）以及它们的故障内的力，我们证明了变形机制的变化是这些观察的起源。高AGEs含量通过AGEs交联而不是通过滑动原胶原分子之间的摩擦来加强力传递。我们发现，这种失败的机制，这是与较低的能量耗散，导致更突然的失败的胶原纤维。我们的研究结果提供了一个直接和因果关系之间的联系增加AGEs含量，抑制纤维内滑动，增加刚度，突然原纤维断裂。因此，他们解释了在老年人和糖尿病人群中常见的骨脆性的机械起源。我们的研究结果有助于更好地理解AGEs含量升高导致组织行为受损的机制，并能够针对特定胶原交联水平的降低采取针对性措施。
英文摘要：
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.
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