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Caracterisation et modelisation de l'organisation morphofonctionnelle du cytosquelette lors des processus de mecanotransduction

Abstract : The cytoskeleton is a dynamic three-dimensional structure, occurring mainly in the cytoplasm. It is involved in various cell processes such as signal transduction. In my research I study the architectural variations of cytoskeletal networks which are associated with signal transduction. This study is twofold. First, a step of characterization of the cytoskeletal architecture. Then, in a modeling step I consider the establishment of this architecture. My research focuses on the intermediate filament networks, because of their physical properties and their sub-cellular organization. The first aim of my work was to develop a characterization of the cytoskeletal networks, more specifically of the architecture of cytokeratin networks (intermediate filaments) in the epithelial cells of the MCF7 human breast cancer cell line. Two approaches, using image analysis procedures, have been developped to account for two different geometry levels. The first approach, based on classical methods of mathematical morphology, takes into account the topology of networks. The second approach, is meant to account for the morphology of filaments. These two approaches were used to segment cytoskeleton networks visualized by immunofluorescence and confocal microscopy. Furthermore, topological and morphological parameters have been computed in order to quantify of the network architecture. This methodology has allowed the characterization of at least three types of architectural patterns which can be associated with specific intracellular locations. These intracellular locations are characterized by whether or not a specific force acts upon the zone: junction related force or nucleus integrity preservation related force. The specific architecture of cytoplasmic intermediate filament network suggests its role in the transfer of signals from the cell environment to the nucleus and in the maintenance of nuclear and cellular integrity. Futhermore, this methodology was used to identify the effect of microgravity weightlessness on the cytoskeleton architecture. Also, it can be generalized to apply to other curvilinear object networks, like angiographies or road networks. The results of the characterization of the cytokeratin architecture have showed that the cytokeratin network is a mechanical environment-dependent structure. Under this issue, I have proposed a mathematic model which describes the morphogenesis and the organization of the cytokeratin network driven by the extracellular mechanical conditions acting on an epithelial cell. The main hypothesis of this model is that the regulation of the cytoskeletal protein synthesis is managed by the mechanical environment. The cytokeratin network responds to the extracellular mechanical environment by specific architectural organization, as a reinforcement mechanism, in order to preserve the cell integrity and mediate the extracellular forces to the nucleus. The model governs simultaneously two processes occurring in the cell: the extracellular mechanical environment and its effects on the intracellular domain, and the building up of cytoskeletal network. Each of them is associated with a system of integro-differential equations. In conclusion, this model proposes the establishment of the cytokeratin network in specific structural organization driven by mechanical conditions. Also, the model has been implemented in order to accomplish three-dimensional simulations and visualizations of specific cytokeratin network architecture for a given set of mechanical conditions.
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https://tel.archives-ouvertes.fr/tel-00002326
Contributor : Stephanie Portet <>
Submitted on : Friday, January 31, 2003 - 4:16:28 PM
Last modification on : Saturday, March 28, 2020 - 2:12:43 AM
Long-term archiving on: : Tuesday, September 11, 2012 - 7:35:10 PM

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  • HAL Id : tel-00002326, version 1

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Stephanie Portet. Caracterisation et modelisation de l'organisation morphofonctionnelle du cytosquelette lors des processus de mecanotransduction. Interface homme-machine [cs.HC]. Université Paris-Diderot - Paris VII, 2001. Français. ⟨tel-00002326⟩

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