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In silico biophysics and rheology of blood and red blood cells in Gaucher Disease
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In silico biophysics and rheology of blood and red blood cells in Gaucher Disease
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Journal Article
In silico biophysics and rheology of blood and red blood cells in Gaucher Disease
2025
Overview
Gaucher Disease (GD) is a rare genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucosylceramide in various cells, including red blood cells (RBCs). This accumulation results in altered biomechanical properties and rheological behavior of RBCs, which may play an important role in blood rheology and the development of bone infarcts, avascular necrosis (AVN) and other bone diseases associated with GD. In this study, dissipative particle dynamics (DPD) simulations are employed to investigate the biomechanics and rheology of blood and RBCs in GD under various flow conditions. The model incorporates the unique characteristics of GD RBCs, such as decreased deformability and increased aggregation properties, and aims to capture the resulting changes in RBC biophysics and blood viscosity. This study is the first to explore the Young’s modulus and aggregation parameters of GD RBCs by validating simulations with confocal imaging and experimental RBC disaggregation thresholds. Through in silico simulations, we examine the impact of hematocrit, RBC disaggregation threshold, and cell stiffness on blood viscosity in GD. The results reveal three distinct domains of GD blood viscosity based on shear rate: the aggregation domain, where the RBC disaggregation threshold predominantly influences blood viscosity; the transition area, where both RBC aggregation and stiffness impact on blood viscosity; and the stiffness domain, where the stiffness of RBCs emerges as the primary determinant of blood viscosity. By analyzing RBC mechanical properties and blood viscosity in relation to bone disease, we find that the RBC aggregation properties, deformability, and blood viscosity, may contribute to its onset. These findings enhance our understanding of how changes in RBC properties impact on blood viscosity and may affect bone health, offering a partial explanation for the bone complications observed in GD patients.
Publisher
Public Library of Science,PLOS,Public Library of Science (PLoS)
Subject
