Rosette margination in blood flow during malaria pathogenesis.

Margination is a physical phenomenon that describes the migration of cells and particles toward vessel walls in blood flow, and thus, it serves as a necessary precondition for the adhesion of particles suspended in blood plasma to the endothelium. In the context of malaria, adhesion of infected red blood cells (iRBCs) to the endothelium is essential for the disease progression, as iRBCs have to evade the removal from the blood circulation in the spleen. Some malaria strains lead to the formation of rosettes, multicellular structures composed of one iRBC surrounded by several adhered healthy RBCs (hRBCs). We employ mesoscopic hydrodynamics simulations and microfluidic experiments to investigate the margination of rosettes in blood flow at various flow rates, volume fractions of hRBCs, and binding strengths between iRBCs and hRBCs. Surprisingly, rosette margination is significantly weaker than that of single iRBCs, suggesting their limited adhesion potential in blood flow. The main reason for poor margination of rosettes is the deformability and dynamics of rosette clusters formed by several hRBCs around one iRBC. Simulation predictions are confirmed by microfluidic experiments. Our results suggest that the main function of rosette formation is not to enhance cytoadhesion to the endothelium, but to keep the iRBCs in the blood flow, at least along straight vessel segments.