Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load
Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load
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DOI：
10.1016/j.actbio.2019.05.068
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发表时间：
2019-08-01
影响因子：
9.7
通讯作者：
Alber, Mark
中科院分区：
文献类型：
--
作者：
Britton, Samuel;Kim, Oleg;Alber, Mark
纤维蛋白是一种粘弹性蛋白质聚合物，可决定血凝块和基于纤维蛋白的生物材料响应生物力学力的变形性和完整性。在这里，使用高分辨率共焦显微镜和最近开发的三维计算模型测试了以前未被注意到的纤维蛋白凝块对外部拉伸载荷的机械响应的结构机制。这种机制是单根纤维的局部应变硬化以及整个网络的整体硬化的基础，它基于先前被忽视的在拉伸载荷下形成的纤维蛋白网络中单根纤维（纵横交错）之间的新生内聚成对相互作用。使用实验获得的拉伸纤维蛋白凝块的 3D 成像证实了重新定向纤维的纤维-纤维交叉的存在。该计算模型使我们能够研究结构细节并量化纤维蛋白凝胶在不同空间尺度拉伸过程中纤维-纤维内聚交叉的机械效应。纤维-纤维内聚接触对拉伸纤维蛋白网络弹性的贡献通过单根纤维刚度、纤维长度、宽度和排列以及整个网络的连接性和密度的变化来表征。结果表明，拉伸的纤维蛋白网络中纤维的新生内聚纵横交错包含一个未被充分认识的重要结构机制，该机制是纤维蛋白对（病理）生理应力的机械反应的基础，决定了血栓和止血疾病（例如心脏病发作和缺血性中风）的过程和结果。意义说明 纤维蛋白是一种粘弹性蛋白质聚合物，决定着血凝块和基于纤维蛋白的生物材料响应生物力学力的变形性和完整性。在本文中，使用高分辨率共聚焦显微镜和新开发的计算模型测试了纤维蛋白凝块对外部拉伸载荷的机械响应的新颖结构机制。这种机制是单根纤维的局部应变硬化以及整个网络的整体硬化的基础，它基于先前被忽视的在拉伸载荷下形成的纤维蛋白网络中单根纤维（纵横交错）之间的新生内聚成对相互作用。内聚纵横交错是一种重要的结构机制，影响血栓的机械反应，并可以决定凝血障碍的结果，例如心脏病发作和中风。 (C) 2019 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Fibrin is a viscoelastic proteinaceous polymer that determines the deformability and integrity of blood clots and fibrin-based biomaterials in response to biomechanical forces. Here, a previously unnoticed structural mechanism of fibrin clots' mechanical response to external tensile loads is tested using high-resolution confocal microscopy and recently developed three-dimensional computational model. This mechanism, underlying local strain-stiffening of individual fibers as well as global stiffening of the entire network, is based on previously neglected nascent cohesive pairwise interactions between individual fibers (crisscrossing) in fibrin networks formed under tensile load. Existence of fiber-fiber crisscrossings of reoriented fibers was confirmed using 3D imaging of experimentally obtained stretched fibrin clots. The computational model enabled us to study structural details and quantify mechanical effects of the fiber-fiber cohesive crisscrossing during stretching of fibrin gels at various spatial scales. The contribution of the fiber-fiber cohesive contacts to the elasticity of stretched fibrin networks was characterized by changes in individual fiber stiffness, the length, width, and alignment of fibers, as well as connectivity and density of the entire network. The results show that the nascent cohesive crisscrossing of fibers in stretched fibrin networks comprise an underappreciated important structural mechanism underlying the mechanical response of fibrin to (patho)physiological stresses that determine the course and outcomes of thrombotic and hemostatic disorders, such as heart attack and ischemic stroke. Statement of Significance Fibrin is a viscoelastic proteinaceous polymer that determines the deformability and integrity of blood clots and fibrin-based biomaterials in response to biomechanical forces. In this paper, a novel structural mechanism of fibrin clots' mechanical response to external tensile loads is tested using high-resolution confocal microscopy and newly developed computational model. This mechanism, underlying local strain-stiffening of individual fibers as well as global stiffening of the entire network, is based on previously neglected nascent cohesive pairwise interactions between individual fibers (crisscrossing) in fibrin networks formed under tensile load. Cohesive crisscrossing is an important structural mechanism that influences the mechanical response of blood clots and which can determine the outcomes of blood coagulation disorders, such as heart attacks and strokes. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.