Sensing from the inside: how the nucleus controls adaptive cell responses to shape deformations
Mechanical forces within the tissue microenvironment influence a multitude of cellular processes and dynamic cell behavior. How cells sense deformations of their shape and regulate cytoskeletal dynamics in response to mechanical forces still remains only poorly understood. We identified that cell confinement can trigger a rapid switch to amoeboid cell migration. This amoeboid cell transformation is mediated by an increase in myosin II-dependent cell contractility. Increased cell contractility promotes mechanical instabilities in the cell cortex, leading to cell polarization and fast amoeboid motility. I will discuss how the cell nucleus functions as a mechano-controller of dynamic cell behavior. We found that nucleus stretch in deformed cells activates a lipase-based mechano-transduction pathway at the inner nuclear membrane that regulates cell contractility. We further showed that nucleus deformation and its intracellular positioning enables cells to measure different types of cell shape changes under mechanical stress. Our data support that the nucleus establishes a functional module for cellular proprioception, enabling cells to decode different types of shape changes and to adapt their behaviour to the 3D microenvironment.