Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
CFisUC, Department of Physics, University of Coimbra, Coimbra, Portugal.
Commun Biol. 2023 Feb 17;6(1):192. doi: 10.1038/s42003-023-04560-4.
Erythrocytes are deformable cells that undergo progressive biophysical and biochemical changes affecting the normal blood flow. Fibrinogen, one of the most abundant plasma proteins, is a primary determinant for changes in haemorheological properties, and a major independent risk factor for cardiovascular diseases. In this study, the adhesion between human erythrocytes is measured by atomic force microscopy (AFM) and its effect observed by micropipette aspiration technique, in the absence and presence of fibrinogen. These experimental data are then used in the development of a mathematical model to examine the biomedical relevant interaction between two erythrocytes. Our designed mathematical model is able to explore the erythrocyte-erythrocyte adhesion forces and changes in erythrocyte morphology. AFM erythrocyte-erythrocyte adhesion data show that the work and detachment force necessary to overcome the adhesion between two erythrocytes increase in the presence of fibrinogen. The changes in erythrocyte morphology, the strong cell-cell adhesion and the slow separation of the two cells are successfully followed in the mathematical simulation. Erythrocyte-erythrocyte adhesion forces and energies are quantified and matched with experimental data. The changes observed on erythrocyte-erythrocyte interactions may give important insights about the pathophysiological relevance of fibrinogen and erythrocyte aggregation in hindering microcirculatory blood flow.
红细胞是可变形的细胞，其经历渐进的生物物理和生化变化，影响正常的血流。纤维蛋白原是血浆中最丰富的蛋白质之一，是血液流变学特性变化的主要决定因素，也是心血管疾病的主要独立危险因素。在这项研究中，通过原子力显微镜（AFM）测量人红细胞之间的黏附，并通过微管吸吮技术观察在纤维蛋白原存在或不存在的情况下的变化。然后，将这些实验数据用于开发一个数学模型，以研究两个红细胞之间的生物医学相关相互作用。我们设计的数学模型能够探索红细胞-红细胞之间的黏附力和红细胞形态的变化。AFM 红细胞-红细胞黏附数据表明，在纤维蛋白原存在的情况下，克服两个红细胞之间黏附所需的功和分离力增加。在数学模拟中成功地跟踪了红细胞形态的变化、细胞间的强黏附和两个细胞的缓慢分离。量化并匹配了红细胞-红细胞黏附力和能量与实验数据。观察到的红细胞-红细胞相互作用的变化可能为纤维蛋白原和红细胞聚集在阻碍微循环血流方面的病理生理学相关性提供重要的见解。
