A mathematical model of fibrinogen-mediated erythrocyte–erythrocyte adhesion

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. Erythrocyte morphological deformations observed in micropipette aspiration assays resultant from fibrinogen enhanced erythrocyte–erythrocyte adhesion are characterised by new mathematical model calibrated by atomic force microscopy measurements.