Advanced-Glycation Endproducts: How cross-linking properties affect the collagen fibril behavior
Advanced-Glycation Endproducts: How cross-linking properties affect the collagen fibril behavior
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DOI：
10.1016/j.jmbbm.2023.106198
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发表时间：
2023-11-08
影响因子：
3.9
通讯作者：
Kammer，David S.
中科院分区：
文献类型：
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作者：
Kamml，Julia;Acevedo，Claire;Kammer，David S.
已知高级糖基化终产物（AGEs）是组织材料特性受损的主要原因。在构成人体组织的主要组成部分的胶原纤维中，这些AGEs表现为纤维状交联。已经表明，当AGEs在胶原纤维中积累时，胶原纤维的机械性质改变，这是通常由糖尿病和衰老引起的过程。然而，由于缺乏可用的实验数据，目前关于不同类型的AGEs的机械性能及其在胶原纤维中的量的知识是有限的。因此，对于不同类型的纳米级交联性质、其在胶原原纤维中的密度以及胶原原纤维在较大尺度下的机械性质之间的精确关系仍然知之甚少。在我们的研究中，我们使用粗粒度的分子动力学模拟和胶原纤维进行破坏性拉伸试验，以评估不同的交联密度和它们的机械性能对胶原纤维的变形和断裂行为的影响。我们观察到，胶原纤维硬化在高应变水平时，无论是AGEs密度或AGEs的负载能量容量增加。基于我们的研究结果，我们表明，这种硬化是由一种有利于通过拉伸而不是分子间滑动吸收能量的机制引起的。因此，在这些交联的胶原原纤维中，吸收的能量被储存而不是通过摩擦耗散，导致原纤维失效时的脆性断裂。此外，通过改变多个AGEs纳米尺度参数，我们表明，AGEs的负载能量容量，除了它们在原纤维中的密度，确定不同类型的AGEs对胶原纤维的机械行为的影响的唯一因素。我们的研究结果表明，了解AGEs的性质是至关重要的，更好地了解受损的组织行为的纳米尺度的起源。我们进一步建议，未来的实验研究应集中在量化的AGEs的负载能量容量作为一个关键属性，他们对胶原纤维的影响。
Advanced-Glycation-Endproducts (AGEs) are known to be a major cause of impaired tissue material properties. In collagen fibrils, which constitute a major building component of human tissue, these AGEs appear as fibrillar cross-links. It has been shown that when AGEs accumulate in collagen fibrils, a process often caused by diabetes and aging, the mechanical properties of the collagen fibril are altered. However, current knowledge about the mechanical properties of different types of AGEs, and their quantity in collagen fibrils is limited owing to the scarcity of available experimental data. Consequently, the precise relationship between the nano-scale cross-link properties, which differ from type to type, their density in collagen fibrils, and the mechanical properties of the collagen fibrils at larger scales remains poorly understood. In our study, we use coarse-grained molecular dynamics simulations and perform destructive tensile tests on collagen fibrils to evaluate the effect of different cross-link densities and their mechanical properties on collagen fibril deformation and fracture behavior. We observe that the collagen fibril stiffens at high strain levels when either the AGEs density or the loading energy capacity of AGEs are increased. Based on our results, we demonstrate that this stiffening is caused by a mechanism that favors energy absorption via stretching rather than inter-molecular sliding. Hence, in these cross-linked collagen fibrils, the absorbed energy is stored rather than dissipated through friction, resulting in brittle fracture upon fibrillar failure. Further, by varying multiple AGEs nano-scale parameters, we show that the AGEs loading energy capacity is, aside from their density in the fibril, the unique factor determining the effect of different types of AGEs on the mechanical behavior of collagen fibrils. Our results show that knowing AGEs properties is crucial for a better understanding of the nano-scale origin of impaired tissue behavior. We further suggest that future experimental investigations should focus on the quantification of the loading energy capacity of AGEs as a key property for their influence on collagen fibrils.