Biophysical determinants of nuclear shape and mechanics and their implications for genome integrity

The nuclear envelope (NE) has a dual role of serving as a protective shell for the genome and a critical communication interface that compartmentalizes cells into cytoplasmic and nuclear domains. The NE is reinforced by the integrated scaffold of nuclear lamins, heterochromatin, nuclear pores, and other NE proteins with critical roles in regulating the three-dimensional architecture of the genome. Importantly, this interface is in the direct path of force transduction, emanating from the cell-extrinsic environment and generated by the cells themselves, leading to deformation of the nucleus. Alterations in the mechanical properties of NE components have profound implications for cellular dysfunction, aging, and disease. Here we discuss some of the recent findings on the biophysical properties of the nuclear periphery and how NE-derived signaling and nuclear remodeling serve as gatekeepers of genome integrity, normal ploidy, and cellular function.