A mathematical model of fibrinogen-mediated erythrocyte–erythrocyte adhesion

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.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.This work was supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) projects PTDC/EMD-TLM/7289/2020 (all authors), PTDC/BBB-BMD/6307/2014 and UID/BIM/50005/2019 (CSL, FAC, NCS), through Fundos do Orçamento de Estado. JC and RT also thank the support of FEDER funds through the Operational Programme Competitiveness Factors – COMPETE and Fundação para a Ciência e a Tecnologia through the strategic projects UIDB/04564/2020 and UIDP/04564/2020. CSL also acknowledges FCT-MCTES fellowships PD/BD/135045/2017 and COVID/BD/151823/2021, General Programme of the European Molecular Biology Conference – EMBO Short-Term Fellowship 8350, and an EBSA Bursary for a working visit to the University of Southern Denmark to perform the micropipette aspiration technique experiments, as well as Erasmus+ mobility – ERASMUS SMT Student Mobility for Traineeships. AH-M acknowledges support from Ministerio de Ciencia e Innovación (Spain) under project PID2019-106063GB-100 and AGAUR (Generalitat de Catalunya) under project 2017 SGR-1061.