Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028, Lisbon, Portugal.
Thrombosis & Tissue Repair Group, Discovery & Translational Science Department, Leeds Institute of Cardiovascular & Metabolic Medicine & Multidisciplinary Cardiovascular Centre, Faculty of Medicine & Health, University of Leeds, Leeds, United Kingdom.
Nanomedicine (Lond). 2018 Oct;13(19):2491-2505. doi: 10.2217/nnm-2018-0136. Epub 2018 Oct 12.
γ' fibrinogen has been associated with thrombosis. Here the interactions between γ'γ' or γAγA fibrinogen and red blood cells (RBCs), and their role on fibrin clot properties were studied.
MATERIALS & METHODS: Atomic Force microscopy (AFM)-based force spectroscopy, rheological, electron and confocal microscopy, and computational approaches were conducted for both fibrinogen variants.
RESULTS & CONCLUSION: AFM shows that the recombinant human (rh)γ'γ' fibrinogen increases the binding force and the frequency of the binding to RBCs compared with rhγAγA, promoting cell aggregation. Structural changes in rhγ'γ' fibrin clots, displaying a nonuniform fibrin network were shown by microscopy approaches. The presence of RBCs decreases the fibrinolysis rate and increases viscosity of rhγ'γ' fibrin clots. The full length of the γ' chain structure, revealed by computational analysis, occupies a much wider surface and is more flexible, allowing an increase of the binding between γ' fibers, and eventually with RBCs.
γ'纤维蛋白原与血栓形成有关。本研究旨在探讨γ'γ'或γAγA 纤维蛋白原与红细胞（RBC）之间的相互作用及其对纤维蛋白凝块性质的影响。
采用原子力显微镜（AFM）基于力谱学、流变学、电子显微镜和共聚焦显微镜以及计算方法对两种纤维蛋白原变体进行了研究。
AFM 结果显示，与 rhγAγA 相比，重组人（rh）γ'γ'纤维蛋白原增加了与 RBC 的结合力和结合频率，从而促进细胞聚集。通过显微镜方法显示，rhγ'γ'纤维蛋白凝块的结构发生变化，呈现出不均匀的纤维蛋白网络。存在 RBC 会降低 rhγ'γ'纤维蛋白凝块的纤溶率并增加其粘度。通过计算分析揭示的全长γ'链结构占据更广泛的表面且更具柔韧性，从而允许γ'纤维之间以及最终与 RBC 之间的结合增加。
