Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biomedical Engineering, Rutgers - The State University of New Jersey, 599 Taylor Road, Room 209, Piscataway, NJ 08854, USA.
J Mech Behav Biomed Mater. 2022 Sep;133:105328. doi: 10.1016/j.jmbbm.2022.105328. Epub 2022 Jun 23.
Blood clots form at the site of vascular injury to seal the wound and prevent bleeding. Clots are in tension as they perform their biological functions and withstand hydrodynamic forces of blood flow, vessel wall fluctuations, extravascular muscle contraction and other forces. There are several mechanisms that generate tension in a blood clot, of which the most well-known is the contraction/retraction caused by activated platelets. Here we show through experiments and modeling that clot tension is generated by the polymerization of fibrin. Our mathematical model is built on the hypothesis that the shape of fibrin monomers having two-fold symmetry and off-axis binding sites is ultimately the source of inherent tension in individual fibers and the clot. As the diameter of a fiber grows during polymerization the fibrin monomers must suffer axial twisting deformation so that they remain in register to form the half-staggered arrangement characteristic of fibrin protofibrils. This deformation results in a pre-strain that causes fiber and network tension. Our results for the pre-strain in single fibrin fibers is in agreement with experiments that measured it by cutting fibers and measuring their relaxed length. We connect the mechanics of a fiber to that of the network using the 8-chain model of polymer elasticity. By combining this with a continuum model of swellable elastomers we can compute the evolution of tension in a constrained fibrin gel. The temporal evolution and tensile stresses predicted by this model are in qualitative agreement with experimental measurements of the inherent tension of fibrin clots polymerized between two fixed rheometer plates. These experiments also revealed that increasing thrombin concentration leads to increasing internal tension in the fibrin network. Our model may be extended to account for other mechanisms that generate pre-strains in individual fibers and cause tension in three-dimensional proteinaceous polymeric networks.
在血管损伤部位形成血栓以密封伤口并防止出血。血栓在执行其生物学功能时会承受张力,同时还要承受血流、血管壁波动、血管外肌肉收缩和其他力的动力学力。有几种机制可以在血栓中产生张力,其中最著名的是由激活的血小板引起的收缩/回缩。在这里,我们通过实验和建模表明,血栓张力是由纤维蛋白聚合产生的。我们的数学模型基于这样的假设:具有二倍对称性和非轴结合位点的纤维蛋白单体的形状最终是单个纤维和血栓中固有张力的来源。随着聚合过程中纤维直径的增大,纤维蛋白单体必须承受轴向扭转变形,以便它们保持在注册状态,形成纤维原纤维特征的半交错排列。这种变形导致预应变,从而导致纤维和网络张力。我们对单根纤维蛋白纤维中预应变的结果与通过切割纤维并测量其松弛长度来测量预应变的实验结果一致。我们使用聚合物弹性的 8 链模型将纤维的力学与网络的力学联系起来。通过将其与可溶胀弹性体的连续体模型相结合,我们可以计算约束纤维蛋白凝胶中张力的演变。该模型预测的时间演化和拉伸应力与在两个固定流变仪板之间聚合的纤维蛋白凝块固有张力的实验测量结果定性一致。这些实验还表明,增加凝血酶浓度会导致纤维蛋白网络中的内部张力增加。我们的模型可以扩展到解释其他在单个纤维中产生预应变并导致三维蛋白质聚合物网络张力的机制。