Dynamic response of cells to viscoelastic forces

ended

Mechanobiology explores how physical forces affect cellular processes, providing insights into areas like embryogenesis and tumor growth. While most studies focus on cells responding to forces stemming from elastic materials, biological materials are viscoelastic. Single materials elastically resist deformation while viscously relaxing with a multitude of relaxation times. Whereas viscoelasticity is increasingly acknowledged in mechanobiology research, its effects on cell behaviour remain poorly understood. This project aims to uncover the mechanisms behind viscoelastic mechanotransduction, by considering cell dynamics and multiple relaxation times within the cell environment. I will engineer hydrogels with tuneable viscoelastic properties, culture fibroblasts on them and employ cutting-edge (live cell) fluorescence microscopy and computational modeling of the cellular mechanotransduction. The hydrogels' elasticity will be tuned by the 3D crosslinked network, and viscosity by linear polymers within the network. Considering properties of gel and force-sensitive proteins inside the cell a stochastic simulation will predict and explain cell behavior, a data-driven model will infer properties from experimentally observed cell behavior. Experimentally, I will characterize mouse fibroblast mechanotransduction on these gels, focusing on adhesion, cytoskeleton, and YAP/TAZ activity, using fluorescent proteins and confocal microscopy. Chemical perturbations of the cytoskeleton will validate the model. Spanning experimental and theoretical methods from material science, cell biology, and computational sciences, this project will shed light on a crucial but underexplored aspect of mechanobiology. As mechanical changes in the cell enviroment are a hallmark of many tumors, this research is particularly relevant for oncology. Further, the models and insights gained will have an impact on the study of organoids in viscoelastic 3D matrices, as well as fibrosis and would healing.