During the intraerythrocytic development, the malaria parasite causes structural, biochemical, and mechanical changes to host red blood cells (RBCs). Major structural changes include the formation of parasitophorus vacuoles that surround the growing parasite in their host RBCs, loss of cell volume, and the appearance of small, nanoscale protrusions or ‘‘knobs,’’ on the membrane surface (1). From the biochemical standpoint, a considerable amount of hemoglobin (Hb) is digested by parasites during intraerythrocytic development and converted into insoluble polymerized forms of heme, known as hemozoin (2,3).
Two major mechanical modifications are loss of RBC deformability (4–6) and increased cytoadherence of the invaded RBC membrane to vascular endothelium and other RBCs (7). These changes lead to sequestration of RBCs in microvasculature in the later stages of parasite development, which is linked to vital organ dysfunction in severe malaria. In the earlier stage, where some loss of deformability occurs, Pf^RBCs continue to circulate in the bloodstream. Membrane dynamics of RBCs can be influenced by human disease states. These changes could provide insights into possible mechanistic pathways in the pathogenesis of malaria, because the parasite alters biophysical properties of RBCs during its intraerythrocyte stage that lasts up to 48 h.