Mechanisms of adhesion-independent cellular mechanosensing

Cells constantly interact with their surrounding and both biochemical and physical stimuli control spatiotemporal cell dynamics and cell function. The ability of cells to probe mechanical properties of their environment and respond to extrinsic mechanical force drives key cellular processes such as cell division, cell differentiation and motility. While accumulating evidence supports a role for cell surface adhesion molecules to integrate and transmit extracellular forces, only little is known about the role of the cortical actomyosin network in cellular mechanosensing. Myosin II molecules are a class of motor proteins that potentially represent a key force--responsive molecular element in the cortical cytoskeleton. In this project we aim to explore molecular details of myosin II--mediated cellular mechanosensing in non--adhesive environments. Using an interdisciplinary approach between cell biology, molecular biology and biophysics will allow for addressing molecular details and regulatory mechanisms of myosin II dynamics under mechanical stress and changing properties of the cortical actomyosin network. In combination with sophisticated imaging tools such as super--resolution single molecule tracking and single cell lattice light sheet microscopy we will derive quantitative molecular information on cortical actomyosin dynamics under extrinsic force loads for establishing a mechanistic model of cellular mechanosensing. Different cell types will be analyzed to identify conserved mechanisms of cellular mechanosensing and unravel signaling pathways that are involved in the regulation of myosin II dependent cellular responses to mechanical stress. The interdisciplinary approach will substantially contribute to our understanding of how cells sense, adapt, and react to extrinsic force and how the fidelity of diverse biological processes such as cell division, polarization and migration is guaranteed under changing physical constraints and mechanical stimuli in various environments.