Density-polarity coupling in confined active polar films: asters, spirals, and biphasic orientational phases

Topological defects in active polar fluids can organise spontaneous flows and influence macroscopic density patterns. Both of them play, for example, an important role during animal development. Yet the influence of density on active flows is poorly understood. Motivated by experiments on cell monolayers confined to discs, we study the coupling between density and polar order for a compressible active polar fluid in presence of a +1 topological defect. As in the experiments, we find a density-controlled spiral-to-aster transition. In addition, biphasic orientational phases emerge as a generic outcome of such coupling. Our results highlight the importance of density gradients as a potential mechanism for controlling flow and orientational patterns in biological systems

Description physique de mécanique cellulaire et tissulaire appliquée à l’étalement de cellules uniques, le bourgeonnement cancéreux et l’extrusion cellulaire

During this PhD, I studied different phenomena pertaining to the mechanics of cells and tissues. The first project describes lamellipodial initiation during cell spreading. The model introduces a coupling between membrane curvature and cortical actin orientation, that generates substrate tractions by friction. A full wetting transition exists when edge curvature, actin orientation and tractions enter into a positive feed-back loop. A bi-stable transition allows a polar nucleation. The second project is an experimental collaboration that studies the way Cancer-Associated Fibroblasts (CAFs) cells could reshape tumours. CAFs surrounding a cluster of Cancer Cells (CCs) assemble a contractile ring to end up on top of CCs, and sometimes build a 3D bud through a shear stress. We use an elasto-plastic model for CAFs, compared with CAF closure dynamics and tractions. We combine vertex and continuous mechanical models to describe the CC monolayer shape, until the appearance of rearrangements. Finally, we describe the mechanical stability of buds by combining elasticity with plastic rearrangements. The last project reports preliminary results on the mechanics of cell extrusion in an epithelial monolayer under compression. Using the same vertex model, we look at the mechanical properties able to drive the basal-to-lateral and lateral-to-apical transitions. Then, we search for a mechanical instability on a minimal 3-cell system, and identify conditions that favour extrusion.Durant ce doctorat, j’ai étudié différents phénomènes liés à la mécanique de cellules et tissus. Le premier projet décrit l’initiation lamellipodiale durant l’étalement cellulaire. Le modèle introduit un couplage entre la courbure membranaire et l’orientation d’actine corticale, qui génère des tractions sur le substrat par friction. Une transition de mouillage total existe quand la courbure du bord, l’orientation d’actine et les tractions entrent dans une boucle rétro-active positive. Une transition bi-stable autorise une nucléation polarisée. Le second projet est une collaboration expérimentale qui étudie comment des Fibroblastes-Associés au Cancer (FACs) pourraient remodeler des tumeurs. Des FACs entourant un amas de Cellules Cancéreuses (CCs) assemblent un anneau contractile pour finir au-dessus des CCs, et génèrent parfois un bourgeon 3D par contrainte de cisaillement. On utilise un modèle élasto-plastique pour les FACs, comparé à la dynamique de fermeture des FACs et les tractions. On combine des modèles mécaniques à «vertex» et continu pour décrire la forme de la monocouche de CCs, jusqu’à l’apparition des réarrangements. Finalement, on décrit la stabilité mécanique des bourgeons en combinant élasticité et réarrangements plastiques. Le dernier projet rapporte des résultats préliminaires sur la mécanique de l’extrusion cellulaire dans une monocouche épithéliale sous compression. Utilisant le même modèle de vertex, on regarde les propriétés mécaniques capables de générer les transitions basal-latéral et latéral-apical. Ensuite, on cherche une instabilité mécanique pour un système minimal à trois cellules, identifiant les conditions qui favorisent l’extrusion

Physical modelling of cell and tissue mechanics applied to single cell spreading, cancerous budding and cell extrusion

Durant ce doctorat, j’ai étudié différents phénomènes liés à la mécanique de cellules et tissus. Le premier projet décrit l’initiation lamellipodiale durant l’étalement cellulaire. Le modèle introduit un couplage entre la courbure membranaire et l’orientation d’actine corticale, qui génère des tractions sur le substrat par friction. Une transition de mouillage total existe quand la courbure du bord, l’orientation d’actine et les tractions entrent dans une boucle rétro-active positive. Une transition bi-stable autorise une nucléation polarisée. Le second projet est une collaboration expérimentale qui étudie comment des Fibroblastes-Associés au Cancer (FACs) pourraient remodeler des tumeurs. Des FACs entourant un amas de Cellules Cancéreuses (CCs) assemblent un anneau contractile pour finir au-dessus des CCs, et génèrent parfois un bourgeon 3D par contrainte de cisaillement. On utilise un modèle élasto-plastique pour les FACs, comparé à la dynamique de fermeture des FACs et les tractions. On combine des modèles mécaniques à «vertex» et continu pour décrire la forme de la monocouche de CCs, jusqu’à l’apparition des réarrangements. Finalement, on décrit la stabilité mécanique des bourgeons en combinant élasticité et réarrangements plastiques. Le dernier projet rapporte des résultats préliminaires sur la mécanique de l’extrusion cellulaire dans une monocouche épithéliale sous compression. Utilisant le même modèle de vertex, on regarde les propriétés mécaniques capables de générer les transitions basal-latéral et latéral-apical. Ensuite, on cherche une instabilité mécanique pour un système minimal à trois cellules, identifiant les conditions qui favorisent l’extrusion.During this PhD, I studied different phenomena pertaining to the mechanics of cells and tissues. The first project describes lamellipodial initiation during cell spreading. The model introduces a coupling between membrane curvature and cortical actin orientation, that generates substrate tractions by friction. A full wetting transition exists when edge curvature, actin orientation and tractions enter into a positive feed-back loop. A bi-stable transition allows a polar nucleation. The second project is an experimental collaboration that studies the way Cancer-Associated Fibroblasts (CAFs) cells could reshape tumours. CAFs surrounding a cluster of Cancer Cells (CCs) assemble a contractile ring to end up on top of CCs, and sometimes build a 3D bud through a shear stress. We use an elasto-plastic model for CAFs, compared with CAF closure dynamics and tractions. We combine vertex and continuous mechanical models to describe the CC monolayer shape, until the appearance of rearrangements. Finally, we describe the mechanical stability of buds by combining elasticity with plastic rearrangements. The last project reports preliminary results on the mechanics of cell extrusion in an epithelial monolayer under compression. Using the same vertex model, we look at the mechanical properties able to drive the basal-to-lateral and lateral-to-apical transitions. Then, we search for a mechanical instability on a minimal 3-cell system, and identify conditions that favour extrusion

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

Abstract During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

Abstract During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro , we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology