Siska Somers

While biochemical and mechanical properties of extracellular matrix (ECM) have well-documented effects on the cell behavior, the cell itself also actively senses and remodels its environment by interacting with ECM components. The forces generated in this bidirectional process are important for normal tissue function and long-distance cell-cell communication and are involved in several pathological conditions such as cancer, fibrosis, atherosclerosis and many more. Despite the growing interest in the field, little is known about the dynamics, spatial distribution, and transmission of cellular forces due to the highly complex nature of the tissue ECM. Understanding mechanotransduction at the molecular level hence requires suitable model systems and novel characterization methods. In this project, we will use synthetic fibrous hydrogels to systematically evaluate the relation between matrix mechanics and cellular forces. Due to their significant role in cancer metastasis, the forces generated by Cancer Associated Fibroblasts (CAFs) will be quantified by recently developed FRET-based DNA-force sensors. The subsequent alterations in the 3D matrix will be visualized by the combination of Stimulated Emission Depletion Microscopy (STED) and Fluorescence Lifetime Imaging Microscopy (FLIM).