Mechanisms of mechanical signal transduction
Mechanical cues impact a wide variety of cellular behaviors, including migration, growth, differentiation, and programmed cell death. We are working to identify mechanical sensor molecules in model cell systems which “read” force-induced deformations of the cytoskeleton and transduce them into biochemical signaling cascades. We aim to visualize these processes in action, both with cellular cryo-EM studies (cryo-electron tomography) and in vitro reconstitution experiments. In the longer term, these efforts are directed towards establishing the underlying molecular mechanisms in sufficient detail to develop them as targets for therapeutic intervention in cancer and regenerative medicine.
Live-cell imaging of mouse embryonic fibroblasts (MEFs) in the presence of cytoskeletal inhibitors shows the LIM protein FHL2's nuclear localization is anti-correlated with tensed actin binding in the cytoplasm. From Sun et al., Dev. Cell, 2020.