Quantifying the biophysical characteristics of Plasmodium-falciparum-parasitized red blood cells in microcirculation

The pathogenicity of Plasmodium falciparum (Pf) malaria results from the stiffening of red blood cells (RBCs) and its ability to adhere to endothelial cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three-dimensional mesoscopic simulations of flow in cylindrical capillaries in order to predict the flow resistance enhancement at different parasitemia levels. In addition, the adhesive dynamics of Pf-RBCs is explored for various parameters revealing several types of cell dynamics such as firm adhesion, very slow slipping along the wall, and intermittent flipping. The parasite inside the RBC is modeled explicitly in order to capture phenomena such as "hindered tumbling" motion of the RBC and the sudden transition from firm RBC cytoadherence to flipping on the endothelial surface. These predictions are in quantitative agreement with recent experimental observations, and thus the three-dimensional modeling method presented here provides new capabilities for guiding and interpreting future in vitro and in vivo studies of malaria.