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IBEC Seminar: Magali Suzanne
martes, junio 20 @ 11:30 am–1:30 pm
Mechanical impact of cell delamination on tissue dynamics, in developmental and tumoral contexts
Centre de Biologie Intégrative, CNRS/UMR 5088, Université Toulouse III, Toulouse, France
How mechanical forces drive morphogenesis is a fundamental question in the field of biomechanics. Combining imaging, genetics, biophysical and modeling approaches, we found that apoptotic cells, far from being eliminated passively, exert a force before dying and thus actively participate in tissue remodeling. This transient force, generated in the depth of the epithelium, constitute a mechanical signal involved in tissue folding. Comparing apoptotic cell dynamics to cells undergoing EMT, we found that a very similar apico-basal force is generated at the onset of EMT.
We further deciphered how these forces are transmitted at the tissue scale through the characterization of a specific mechanical state favoring directional force transmission and developed a new method that offers the opportunity to extract automatically, in strongly deformed epithelia, a precise characterization of the spatial organization of a given cytoskeletal network combined to morphological quantifications in highly remodeled 3D epithelial tissues.
In parallel, we turned to cancer mechanics, focusing particularly in tumor progression. Cancer is a largely widespread pathology that corresponds to an overproliferation of cells that could finally invade others tissues. Tumors develop through three increasingly aggressive steps: (1) hyperplasia, which corresponds to cells overproliferation; (2) dysplasia, during which cells can acquire a more mesenchymal phenotype, and finally (3) metastasis. Tumor development can be influenced by mutations but also by external factors, such as extracellular matrix rigidity. However, a comprehensive understanding of the intrinsic factors driving tumor evolution is still lacking. Our recent unpublished work identifies unexpected factors that could influence tumor development, and more specifically the hyperplasia/dysplasia transition, a critical step in tumor aggressiveness. This work highlights puzzling differences between developmental and tumoral mechanics.