Entry of the malaria parasite merozoite, the micron sized cell responsible for blood-stage malaria infection, into the human red blood cell defines establishment of malaria disease. The process is rapid yet contains a great depth of cell biology, one eukaryotic cell actively penetrating the other. Entry has long been seen as a very parasite-centric process with the merozoite literally driving its way into a passive erythrocyte. This is in marked contrast to other pathogens that utilise host-cell phagocytosis to gain entry to human cells. Has this inbalanced view been over-stated in the case of the merozoite? Recent data from several groups suggests that erythrocyte biophysics (including membrane biophysical properties) also contributes to the process of merozoite entry. Here, I will present our latest insights into the role of both parasite and host cell factors and how they might be contributing to lowering the energy barrier required to get the merozoite inside the human red blood cell. With a particular focus on cell imaging, I will present our vision of invasion being a balanced equation with parasite motor force and host membrane deformability both contributing to allow the blood-stage malaria parasite (and may be beyond the blood stages) get in.
