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Abstract

Biological cells use physical force to interact with their environment, with dramatic consequences for survival, proliferation, differentiation and migration. Force is generated mainly by the contractile actomyosin cytoskeleton and propagated through cell-matrix and cell-cell adhesions. In this thesis, I use finite element methods to model adherent cells as thin active viscoelastic solids to study the dynamics of active force-generation in single cells and force propagation in small cell clusters. The theoretical models are complemented by experiments in which optogenetic activation of the Rho-pathway is combined with traction force microscopy and adhesive micropatterning. For single cells on circular micropatterns, we find perfect homeostasis with a setpoint that strongly depends on cell size and cytoskeletal organization. For epithelial cells, we find that the responder cells actively respond to generate a similar contractile stress as the sender cells, and that force generation and propagation again strongly depends on cytoskeletal organization. Finally, a discontinuous Galerkin method is used to couple the biochemistry of signaling pathways to cell contractility. Overall, our work shows that the active mechanics of adherent cells is strongly modulated by their internal organization, which in turn depends on the adhesive geometry of their environment, thus generating a tightly integrated mechanochemical feedback loop that allows for high-level control structures.