RBC membrane biomechanics and Plasmodium falciparum invasion: probing beyond ligand–receptor interactions

A critical step in malaria blood-stage infections is the invasion of red blood cells (RBCs) by merozoite forms of the Plasmodium parasite. Much progress has been made in defining the parasite ligands and host receptors that mediate this critical step. However, less well understood are the RBC biophysical determinants that influence parasite invasion. In this review we explore how Plasmodium falciparum merozoites interact with the RBC membrane during invasion to modulate RBC deformability and facilitate invasion. We further highlight RBC biomechanics-related polymorphisms that might have been selected for in human populations due to their ability to reduce parasite invasion. Such an understanding will reveal the translational potential of targeting host pathways affecting RBC biomechanical properties for the treatment of malaria.