The influence of AGEs and enzymatic cross-links on the mechanical properties of collagen fibrils
The influence of AGEs and enzymatic cross-links on the mechanical properties of collagen fibrils
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DOI：
10.1016/j.jmbbm.2023.105870
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发表时间：
2023-05-06
影响因子：
3.9
通讯作者：
Kammer, David S.
中科院分区：
文献类型：
--
作者：
Kamml, Julia;Ke, Chun-Yu;Kammer, David S.
胶原蛋白是各种组织的主要组成成分之一，它的机械性能直接来自于其交联型原胶原分子的结构。交联被认为是胶原纤维的关键成分，因为它们可以通过各种方式改变纤维的行为。例如，酶交联物(ECL)是一种特殊类型的交联物，众所周知，它可以稳定原纤维的结构和改善材料性能，而已证明交联型AGEs(高级糖基化终产物)会积累和损害胶原组织的机械性能。然而，一种特定类型的交联剂是否以及如何改善或损害材料性能的原因仍不清楚，并且交联剂性能和密度以及纤维行为之间的确切关系仍然不是很清楚。在这里，我们使用粗粒转向分子模型来评估AGEs和ECLS交联物含量对胶原纤维变形和破坏特性的影响。我们的模拟表明，当AGEs含量超过临界值时，胶原纤维在高应变水平下变硬。此外，纤维的强度随着年龄的积累而增加。通过分析不同类型的交联体(AGE和ECL)内的力以及它们的破坏，我们证明了变形机制的改变是这些观察到的根源。高含量的AGEs通过AGEs交联链而不是通过滑动的原胶原分子之间的摩擦来加强力传递，这会导致原胶原分子内的键断裂而失败。我们发现，这种破坏机制与较低的能量消耗有关，导致胶原原纤维更加突然的破坏。我们的结果提供了AGEs含量增加、抑制纤维内滑动、僵硬增加和突然的纤维骨折之间的直接和因果联系。因此，他们解释了在老年人和糖尿病人群中普遍观察到的骨脆性的机械起源。我们的发现有助于更好地理解由于AGEs含量增加而导致组织行为受损的潜在机制，并可能实现关于降低特定胶原交联度的有针对性的措施。
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.