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

PLoS Pathog. 2024 Jul 25;20(7):e1012392. doi: 10.1371/journal.ppat.1012392. eCollection 2024 Jul.

Abstract

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.

MeSH terms

  • Actins / metabolism
  • Cell Adhesion / physiology
  • Cell Movement* / physiology
  • Entamoeba histolytica* / metabolism
  • Entamoeba histolytica* / physiology
  • Entamoebiasis / metabolism
  • Entamoebiasis / parasitology
  • Fibronectins* / metabolism
  • Humans
  • Podosomes / metabolism
  • Protozoan Proteins / metabolism

Substances

  • Fibronectins
  • Actins
  • Protozoan Proteins

Grants and funding

JC. OM got grants from the Labex IBEID (ANR-10-LABX-62-IBEID), France-BioImaging (ANR-10-INBS-04), the PIA INCEPTION program (ANR-16-CONV-0005) and HORIZON-HLTH-2021-DISEASE (H2020 HLTH DI-DIDA). E.L got the Emulate Carnot Pasteur Medecin Santé call and the Institut Pasteur 232 PTR grant (PTR Mechabiome). The UTechS PBI is supported by the French National Research Agency (France BioImaging; ANR-10–INBS–04; Investments for the Future). G.L. was a master student at Sorbonne University supported by Erasmus+. A.BP was supported by the Institut Pasteur through the 232 PTR grant Mechabiome. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.