Mechanical regulation and activity of nuclear condensates

The cell nucleus is constantly subjected to forces under many fundamental biological processes, including confined cell migration, osmoregulation, and large-scale stresses across tissues during development. Biomolecular condensates, a class of subcellular structures without surrounding membranes, are responsive to external force perturbation, as seen in early work on germline p-granules nearly two decades ago. However, how external forces on cells impact physiological condensation at the subcellular level, and how condensates themselves can be mechanically active, is still an emerging area of research. Here, we discuss recent advances in mechanochemical regulation of phase-separation events, focusing primarily within the cell nucleus. We also discuss open questions about how biomolecular condensates may play a role in cell mechanics and function in response to external forces.