Glycation cross-linking induced mechanical-enzymatic cleavage of microscale tendon fibers
Glycation cross-linking induced mechanical-enzymatic cleavage of microscale tendon fibers
复制标题
DOI：
10.1016/j.matbio.2013.11.005
复制
发表时间：
2014-02-01
期刊：
影响因子：
6.9
通讯作者：
Torzilli, Peter A.
中科院分区：
文献类型：
--
作者：
Bourne, Jonathan W.;Lippell, Jared M.;Torzilli, Peter A.
最近使用胶原蛋白肽的分子建模数据预测，通过分子间交联传递的机械力导致胶原蛋白三螺旋解绕。这些模拟进一步预测了这种被称为三螺旋微折叠的解绕，发生在远低于典型胶原损伤机制的力下。在很大程度上基于这些数据，我们假设糖基交联肌腱微纤维的机械负荷会导致加速的胶原溶解酶损伤。这一假设与文献报道形成鲜明对比，文献报道表明单独的机械负荷或交联各自延缓胶原底物的酶降解。使用我们的胶原酶机械动力学自动测试（CEMKAT）系统，我们机械加载了与糖化学交联的富含胶原的肌腱微纤维，并测试了降解酶的敏感性。我们的研究结果表明，交联纤维在卸载时对酶降解的抵抗力提高了5倍，但当它们被施加机械变形拉伸时，就变得非常容易受到酶裂解的影响。(C) 2013 Elsevier B.V.版权所有
Recent molecular modeling data using collagen peptides predicted that mechanical force transmitted through intermolecular cross-links resulted in collagen triple helix unwinding. These simulations further predicted that this unwinding, referred to as triple helical microunfolding, occurred at forces well below canonical collagen damage mechanisms. Based in large part on these data, we hypothesized that mechanical loading of glycation cross-linked tendon microfibers would result in accelerated collagenolytic enzyme damage. This hypothesis is in stark contrast to reports in literature that indicated that individually mechanical loading or cross-linking each retards enzymatic degradation of collagen substrates. Using our Collagen Enzyme Mechano-Kinetic Automated Testing (CEMKAT) System we mechanically loaded collagen-rich tendon microfibers that had been chemically cross-linked with sugar and tested for degrading enzyme susceptibility. Our results indicated that cross-linked fibers were >5 times more resistant to enzymatic degradation while unloaded but became highly susceptible to enzyme cleavage when they were stretched by an applied mechanical deformation. (C) 2013 Elsevier B.V. All rights reserved.