α-α Cross-Links Increase Fibrin Fiber Elasticity and Stiffness
α-α Cross-Links Increase Fibrin Fiber Elasticity and Stiffness
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DOI：
10.1016/j.bpj.2011.11.4016
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发表时间：
2012-01-04
影响因子：
3.4
通讯作者：
Guthold, Martin
中科院分区：
文献类型：
--
作者：
Helms, Christine C.;Ariens, Robert A. S.;Guthold, Martin
纤维蛋白纤维的直径约为 100 nm，是血凝块的主要结构成分。单纤维蛋白纤维的机械特性决定了血凝块的行为，因此对心脏病、中风和栓塞具有至关重要的影响。交联被认为可以强化血栓。然而，α-α交联在纤维蛋白纤维组装中的作用及其对单纤维蛋白纤维机械性能的影响知之甚少。为了解决这一知识差距，我们使用荧光和原子力显微镜相结合的技术来确定单个、未交联、完全 α-α 交联（γ Q398N/Q399N/K406R 纤维蛋白原变体）和完全交联纤维蛋白纤维的刚度（模量）、延展性和弹性。与未交联的纤维相比，独特的 α-α 交联使纤维的硬度提高 2.5 倍，弹性提高 1.5 倍，而完全交联则使纤维的硬度提高 3.75 倍，弹性提高 1.2 倍，但可延展性降低 1.2 倍。根据这些结果和文献数据，我们提出了一个模型，其中 α-C 区域在纤维蛋白分子和原纤维的相互连接和内连接中发挥重要作用，赋予纤维蛋白纤维增加的刚度和弹性。
Fibrin fibers, which are similar to 100 nm in diameter, are the major structural component of a blood clot. The mechanical properties of single fibrin fibers determine the behavior of a blood clot and, thus, have a critical influence on heart attacks, strokes, and embolisms. Cross-linking is thought to fortify blood clots; though, the role of alpha-alpha cross-links in fibrin fiber assembly and their effect on the mechanical properties of single fibrin fibers are poorly understood. To address this knowledge gap, we used a combined fluorescence and atomic force microscope technique to determine the stiffness (modulus), extensibility, and elasticity of individual, uncross-linked, exclusively alpha-alpha cross-linked (gamma Q398N/Q399N/K406R fibrinogen variant), and completely cross-linked fibrin fibers. Exclusive alpha-alpha cross-linking results in 2.5x stiffer and 1.5x more elastic fibers, whereas full cross-linking results in 3.75x stiffer, 1.2x more elastic, but 1.2x less extensible fibers, as compared to uncross-linked fibers. On the basis of these results and data from the literature, we propose a model in which the alpha-C region plays a significant role in inter- and intralinking of fibrin molecules and protofibrils, endowing fibrin fibers with increased stiffness and elasticity.