%0 Generic
%A Drozdowski, Oliver Max
%C Heidelberg
%D 2025
%F heidok:35639
%R 10.11588/heidok.00035639
%T Theory of force generation in polarized biological systems
%U https://archiv.ub.uni-heidelberg.de/volltextserver/35639/
%X The ability of biological cells to generate physical force is essential for many cell-scale processes, including adhesion, migration and division. It is also pivotal for many multicellular processes, such as embryogenesis and wound closure. Force generation by cells and tissues is naturally linked to polarization, both being vectorial processes that can be coupled easily. In this thesis concepts and methods from theoretical physics are used to study force generation in polarized biological systems on multiple scales. For single contractile cells, the theory of active gels is extended by incorporating the van-der-Waals-type behavior of contractile myosin motor proteins, yielding a nonlinear diffusion coefficient. This minimal theory explains the spontaneous symmetry breaking between sessile and migratory states, as observed for example in optogenetic experiments, and shows the importance of polarized contractions for biological function. For multicellular sheets with apico-basal polarity, computer simulations of vertex models and continuum mechanics are combined to show that morphological transitions and cell extrusion occur at topological defects, coupling forces on the tissue and single-cell scale. For organoids, a three dimensional reconstruction and cellular force inference method is developed, combining artificial-intelligence-based image processing and the statistics of point clouds. By applying this method on experimental data, intestinal organoids are shown to undergo tissue-scale budding because of apico-basally polarized contractile cellular forces. Finally, for retinal organoids injected with morphogen-carrying DNA-hydrogel beads, it is predicted how morphogens, determining cell fate and thus potential force patterning, disperse in organoids. This work demonstrates how polarized force generation inside biological cells leads to the emergence of complex mechanics on larger scales.