Formation of Pattern and Shape in Confined Cellular Systems

This theoretical project aims to develop a conceptual and quantitative understanding of self-organized protein pattern formation and dynamics of cells and tissues. We will study these questions at two different levels of coarse-graining: at the cellular and the intracellular level. To understand the response of single cells and assemblies of cells to external stimuli and spatial confinement we will use and further extend the Cellular Potts Model that we have continuously developed and extended over the last funding periods. Generalizations will include the effect of spatial confinement, substrate rigidity, internal regulatory processes, as well as applications to organoids. In parallel, we will investigate the role of geometry, spatial organization, and molecular interactions on protein pattern formation. We will generalize our conceptual studies of mass-conserving reaction-diffusion systems to understand wave length selection, the role of geometric constraints, bulk-surface coupling, cytoplasmic flows, and multi-species systems. Furthermore, we will develop quantitative and predictive models for specific experimental studies on the Min system in confined geometry. In a new line of research, we will extend our analysis towards mechano-chemical systems where chemical patterns are interlinked with mechanical deformations of the membrane (cortex), cytoplasmic flow, and cytoskeletal dynamics. Finally, we will explore possible mechanisms underlying pattern-induced cargo transport.