Modeling Transmigration of Malaria Infected Red Blood Cells through Inter-Endothelial Slits in Human Spleens using Dissipative Particle Dynamics

Abstract

We simulate the transmigration of malaria-infected red blood cells (RBCs) through the inter-endothelial slits in the human spleen by using Dissipative Particle Dynamics based two-component RBC model. We modeled the spectrin-actin network and the lipid bilayer separately and considered the real number of the structural proteins in the model. The mechanical properties of the bilayer-cytoskeletal interactions, such as stiffness and friction, are calibrated by comparing with membrane fluctuations and tank-treading experiments. First, we further validated our numerical model by comparing the predicted retention rates of healthy and pathological cells in an ‘artificial spleen’ consisting of micro beads with the experimental measurements. To explore the possibility of the bilayer-cytoskeletal detachment during this transmigration process, which is strongly related to RBC aging and hereditary spherocytosis, we predicted the maximum interaction force between the spectrin-actin cytoskeleton and the lipid bilayer and compared the value with the previously predicted bilayer-cytoskeletal bond strength. Furthermore, we systematically studied the effects of cell rigidity, cell shape and inter-endothelial slit dimensions on the critical pressure gradient for RBCs to pass through the spleen. We found that the cell shape plays a much more important role than the cell rigidity in the transmigration process, which may guide the future experiments and the drug design for eradicating malaria and treating anemia such as hereditary spherocytosis.