Wall Shear Stress-Based Model for Adhesive Dynamics of Red Blood Cells in Malaria

Abstract

Red blood cells (RBCs) infected by the Plasmodium falciparum (Pf-RBCs) parasite lose their membrane deformability and they also exhibit enhanced cytoadherence to vascular endothelium and other healthy and infected RBCs. The combined effect may lead to severe disruptions of normal blood circulation due to capillary occlusions. Here we extend the adhesion model to investigate the adhesive dynamics of Pf-RBCs as a function of wall shear stress (WSS) and other parameters using a three-dimensional, multiscale RBC model. Several types of adhesive behavior are identified, including firm adhesion, flipping dynamics, and slow slipping along the wall. In particular, the flipping dynamics of Pf-RBCs observed in experiments appears to be due to the increased stiffness of infected cells and the presence of the solid parasite inside the RBC, which may cause an irregular adhesion behavior. Specifically, a transition from crawling dynamics to flipping behavior occurs at a Young's modulus approximately three times larger than that of healthy RBCs. The simulated dynamics of Pf-RBCs is in excellent quantitative agreement with available microfluidic experiments if the force exerted on the receptors and ligands by an existing bond is modeled as a nonlinear function of WSS.