Using Kinematics and modeling to decipher how Toxoplasma parasites apply force to invade host cells

A major interest of my lab is to delve deeper into the molecular machinery that drives Toxoplasma tachyzoites into their host cells with a primary focus on force production during the process. To decipher the origin and feature of the force(s) powering parasite entry, we combined kinematic and modeling analysis of cell invasion using parasites that express a fluorescent and functional version of RON2, the core component of the critical parasite-zoite junction. We showed that the majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction. However, when the parasites encounter resistance in their way in or when the junction is not properly anchored to the host cell cortex, the junction is instead capped backwards together with the host cell membrane to eventually enclose the parasite in a functional vacuole. kinematic analysis allowed to demonstrate a similar parasite driven force controlling static and capped junction scenarios. Next, we have compared the effect of (i) a stronger defect in junction anchorage by a motor-competent tachyzoite and of (ii) a deficiency of myosin motor in tachyzoites and we will present data showing that both lead to invasion success or failure but with distinct sequences and consequences.
Overall, our detailed live imaging analysis has allowed better phenotype assessment of mutants for proteins involved during invasion and has provided new evidence that (i) tachyzoites need to engage myosin motor with the junction molecular complex to promote force production (ii) this sequence depends on the anchorage of the junction to the host cell cortex.