Cells must constantly sense and respond to physical forces from their environment in order to migrate, differentiate, and proliferate. These processes are critical for diverse cell functions, including growth, wound healing, and immune responses. The cytoskeleton - a complex and dynamic network of protein filaments - acts as a cell’s structural framework, determining its shape, organising its intracellular components, and enabling its movement and division. While the pivotal role of cytoskeleton in responding to external forces is well recognised, the mechanisms by which these mechanical signals are transmitted to the nucleus to influence cell behaviour have remained unclear.
The research team have evidenced an ATR-RASSF1A signalling cascade that is activated by mechanical forces, allowing mechanical coupling of the cytoskeleton with the nuclear envelope. This newly uncovered pathway stabilises nuclear actin, protecting the nucleus during cell motility and compression.