Soutenance de thèse Aziza Merzouki
Mme Aziza Merzouki soutiendra en anglais, en vue de l'obtention du grade de docteur ès sciences, mention informatique, sa thèse intitulée:
Numerical Modelling of Confluent Cell Monolayers :
Date: Vendredi 4 mai 2018 à 10h00
Lieu: CUI / Battelle bâtiment A, auditoire rez-de-chaussée
- Prof. Jaap Kaandorp (University of Amsterdam)
- Prof. Michel Milinkovitch (Université de Genève)
- Prof. Aurélien Roux (Université de Genève)
- Dr. Orestis Malaspinas (HEPIA)
- Prof. Bastien Chopard (Université de Genève)
Our objective in this work is to develop and implement a numerical model of confluent cell monolayers to study the relation between cell biophysical properties on the one hand and tissue mechanics and morphology on the other hand. We want the model to be cell-based and to combine both physics and biology, allowing us to represent cell mechanical properties, externalmechanical constraints, stress and strains, as well as cell proliferation and signalling. We focused on a vertex-model, initially inspired from Farhadifar et al. 2007, which we implemented, modified and extended. This model was used in the context of different studies and collaborations.
We investigated how the cell mechanical properties, namely their apical contractility and intercellular adhesion, affect the response of tissues to stretching. We compared our simulations of tissue stretching to the experiments of Harris et al. 2012 and calibrated our model parameters so that our numerical results match the experimental measurements. This allowed us to show how tissue stretching may trigger a change in cell mechanical properties.
We studied the development of the spine follicles of Acomys Dimidiatus (also called spiny mouse). We focused on the mechanisms that shape the spine follicles. We investigated the factors that drive the Dermal Papilla (DP) cells, located at the center of the follicle, to flatten and slightly off-center between the embryonic stages E32 and E36 (32 and 36 days after fertilisation), whileMatrix cells at the periphery of the follicle proliferate yielding an enlarged follicle.
We also used the vertexmodel to study tissue buckling. We simulated cross-sections of circular cell-monolayers and showed how cell mechanics affect the geometry and the relaxation times of cell monolayers, which are characteristic of buckling tissues. We showed that it is the competition between the cell monolayer relaxation and the cell proliferation that controls the buckling of unconstrained tissues.
In the context of our collaboration with the Roux Lab, where epithelial cell monolayers are cultured inside hydrogel microcapsules, we also investigated the folding of simulated tissues growing inside elastic environments.
Finally, we extended our initial 2D model to the 3D space and presented its application for the study of tissue folding.