Abstract
Cells generate and sense mechanical forces that trigger biochemical signals to elicit cellular responses that control cell fate changes. Mechanical forces also physically distort neighboring cells and the surrounding connective tissue, which propagate mechanochemical signals over long distances to guide tissue patterning, organogenesis, and adult tissue homeostasis. As the largest and stiffest organelle, the nucleus is particularly sensitive to mechanical force and deformation. Nuclear responses to mechanical force include adaptations in chromatin architecture and transcriptional activity that trigger changes in cell state. These force-driven changes also influence the mechanical properties of chromatin and nuclei themselves to prevent aberrant alterations in nuclear shape and help maintain genome integrity. This review will discuss principles of nuclear mechanotransduction and chromatin mechanics and their role in DNA damage and cell fate regulation.