Mechanical Forces in Nuclear Organization

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. MECHANICAL FORCES IN CELLS AND TISSUEST issue and cell dynamics and movement gen- erate physical forces, including compression or stretching, which are transferred to the nucleus and chromatin, resulting in their deformation.Substantial deformation occurs not only in mechanically active tissues, such as the muscle, where cells and nuclei are directly exposed to constant contractile forces, but also in tissues such as the lung, skin, and vasculature whose surface area changes during respiration, body motion, and blood flow (Fig. 1).In addition to these high-amplitude changes that affect the tissue as a whole, most cells experience deformation at smaller scales.For instance, cell migration, especially within confined spaces of the connective tissue, causes substantial cell deformation (Friedl et al. 2011).