Fibronectin induces a transition from amoeboid to a fan morphology and modifies migration in Entamoeba histolytica.

Cell migration modes can vary, depending on a number of environmental and intracellular factors. The high motility of the pathogenic amoeba Entamoeba histolytica is a decisive factor in its ability to cross the human colonic barrier. We used quantitative live imaging techniques to study the migration of this parasite on fibronectin, a key tissue component. Entamoeba histolytica amoebae on fibronectin contain abundant podosome-like structures. By using a laminar flow chamber, we determined that the adhesion forces generated on fibronectin were twice those on non-coated glass. When migrating on fibronectin, elongated amoeboid cells converted into fan-shaped cells characterized by the presence of a dorsal column of F-actin and a broad cytoplasmic extension at the front. The fan shape depended on the Arp2/3 complex, and the amoebae moved laterally and more slowly. Intracellular measurements of physical variables related to fluid dynamics revealed that cytoplasmic pressure gradients were weaker within fan-shaped cells; hence, actomyosin motors might be less involved in driving the cell body forward. We also found that the Rho-associated coiled-coil containing protein kinase regulated podosome dynamics. We conclude that E. histolytica spontaneously changes its migration mode as a function of the substrate composition. This adaptive ability might favour E. histolytica's invasion of human colonic tissue. By combining microfluidic experiments, mechanical modelling, and image analysis, our work also introduces a computational pipeline for the study of cell migration. Author summary: Even though we know increasingly well how cells move in tissues, the question of whether parasites modify their migration as a function of the host tissue environment requires further investigation. Cell motility is triggered by environmental stimuli, and the migration mode depends on adhesion, activated enzymatic pathways, and changes in the actin cytoskeleton dynamics and thus cell morphology. The protozoan intestinal parasitic Entamoeba histolytica is the causative agent of amoebiasis (a major food- and water-borne disease) in humans. During invasion of the colon, E. histolytica degrades the mucus layer, adheres to and removes the epithelium, progresses along the fibronectin-rich basement membrane towards the crypts of Lieberkühn, and penetrates the mucosa. This invasive process raises the question of how the parasite moves in a varying intestinal environment. E. histolytica is known to display an amoeboid migration mode and binds fibronectin through podosome adhesion structures. We hypothesized that fibronectin triggers signalling pathways that influence the trophozoite's migration. We found that E. histolytica can migrate with a non-amoeboid mode on fibronectin-coated glass. Our finding suggests that for tissue invasion, E. histolytica's migration mode is modulated to suit the environment. [ABSTRACT FROM AUTHOR]