Dynamics and forces during first stages of Entamoeba tissue invasion

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Parasitic amoebae can cause severe diseases, including amoebiasis and amoeba encephalitis. For the progression of diseases caused by amoeba, tissue invasion and destruction are essential. These processes include the passage of amoeba cells through constrictions in the tissue by active motion, the destruction of the extracellular matrix, the killing of target-cells and trogocytosis, i.e., the gnawing of amoeba on target-cells. Hence, both biochemical and physical mechanisms are involved in the first stages of tissue invasion. By combining experimental methods from biophysics and materials science with theoretical approaches from statistical physics, we plan to understand the respective impact of such physical versus biochemical mechanisms in Entamoeba. To do so, we will set up microstructured environments to investigate the impact of confinement on the motion of Entamoeba cells and thus on tissue invasion. Moreover we will monitor if changes of this intracellular motion occur when the Entamoeba approach target-cells. To investigate whether the biological function and pathogenic potential of the amoebae depends on intracellular motion, we will inject tracers to quantify local flow fields and to artificially crowd the intracellular space in order to see if and to what extent intracellular crowding controls (intra)cellular motion. From these measurements and tools from statistical physics we will gain detailed insights into the correlation of motion of and inside the amoeba. In addition, we will also delineate the impact of forces during trogocytosis and tissue destruction, e.g., by traction force microscopy. To gain a deeper understanding of Entamoeba motion in constrictions and when approaching target-cells we will simulate minimal models for amoeba cells using actively moving hard core-soft shell particles. Comparing the exact motion patterns of these squishy model cells with the experimental information we will be able to gauge the involved physical parameters such as the force exerted by the amoeba cells, as well as gain insight into the main guiding principles of Entamoeba motion. In the long run we plan to extend our studies to organ-on-a-chip systems to understand the physical principles of Entamoeba invasion in situations closer to the in vivo situation.