Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Molecular and Nanoscale Physics Group, School of Physics, University of Leeds, Leeds, UK.
J Thromb Haemost. 2022 Jan;20(1):6-16. doi: 10.1111/jth.15531. Epub 2021 Sep 26.
Polymeric fibrin displays unique structural and biomechanical properties that contribute to its essential role of generating blood clots that stem bleeds. The aim of this review is to discuss how the fibrin clot is formed, how protofibrils make up individual fibrin fibers, what the relationship is between the molecular structure and fibrin biomechanical properties, and how fibrin biomechanical properties relate to the risk of thromboembolic disease. Fibrin polymerization is driven by different types of bonds, including knob-hole interactions displaying catch-slip characteristics, and covalent crosslinking of fibrin polypeptides by activated factor XIII. Key biophysical properties of fibrin polymer are its visco-elasticity, extensibility and resistance to rupture. The internal packing of protofibrils within fibers changes fibrin biomechanical behavior. There are several methods to analyze fibrin biomechanical properties at different scales, including AFM force spectroscopy, magnetic or optical tweezers and rheometry, amongst others. Clinically, fibrin biomechanical characteristics are key for the prevention of thromboembolic disorders such as pulmonary embolism. Future studies are needed to address unanswered questions regarding internal molecular structure of the fibrin polymer, the structural and molecular basis of its remarkable mechanical properties and the relationship of fibrin biomechanical characteristics with thromboembolism in patients with deep vein thrombosis and ischemic stroke.
聚合纤维蛋白显示出独特的结构和生物力学特性，这使其在止血方面发挥着至关重要的作用。本文旨在讨论纤维蛋白凝块是如何形成的，原纤维如何构成单个纤维蛋白纤维，分子结构与纤维蛋白生物力学特性之间的关系，以及纤维蛋白生物力学特性与血栓栓塞性疾病风险之间的关系。纤维蛋白的聚合是由不同类型的键驱动的，包括具有“捕捉-滑动”特性的扣眼相互作用，以及激活的因子 XIII 对纤维蛋白多肽的共价交联。纤维蛋白聚合的关键生物物理特性包括粘弹性、可拉伸性和抗破裂性。纤维内原纤维的内部排列改变了纤维蛋白的生物力学行为。有几种方法可以在不同的尺度上分析纤维蛋白的生物力学特性，包括原子力显微镜力谱法、磁性或光学镊子和流变仪等。临床上，纤维蛋白的生物力学特征是预防肺栓塞等血栓栓塞性疾病的关键。未来的研究需要解决关于纤维蛋白聚合物的内部分子结构、其显著机械性能的结构和分子基础以及纤维蛋白生物力学特性与深静脉血栓形成和缺血性中风患者血栓栓塞之间关系的未解决问题。
