Modélisation du comportement mécanique de la cellule et de son cytosquelette : approche basée sur la mécanique des milieux divisés

  • Milan Jean-Louis

  • Microtubules
  • Intermediate filaments
  • Cytoskeleton Cell signal transduction

THESE

The mechanical behavior of living cells, which helps control their biological activity, is closely linked to the mechanical properties of their cytoskeleton (CSK). To describe the prestressed, multi-modular structure of the CSK and its dynamic reorganization, I developed a 2D numerical mechanical model based on the theory of divided media: the CMD (Cytoskeleton - Divided Media) model. The intracellular force systems generated by the various filament networks of the CSK are reproduced in the CMD model by networks of tension and compression interactions established between the nodes of the divided medium making up the model. The special feature of the CMD model is that it proposes a dynamic reorganization mode for the CSD, based on a variable connectivity of the interaction networks that changes to adapt to loading; this reorganization makes it possible to translate the local rearrangements of the CSQ filaments during deformation. The CMD model reproduces the stiffening behavior observed experimentally in cells undergoing deformation, which is a function of the level of CSK contractility. In addition, the interaction networks that develop and balance within the CMD model enable us to identify the different substructures of the CSK: the cortex, the tension fiber network connected to the extracellular matrix via adhesion focal points, the diffuse actin filament network, the intermediate filament network and the microtubule network. Removal of any of these interaction networks leads to a reduction in prestress and stiffness in the model, resulting in a loss of structural integrity, suggesting that CSK substructures are highly interdependent. In view of these results, the CMD model may provide a tool for understanding cellular processes involving CSK reorganization, such as adhesion, migration or mechanotransduction.