Nuclear confinement by perinuclear actin network causes chromatin herniation and NE rupture. (A) In cells cultured on rigid substrates, contractile actin fibers spanning the nucleus compress the nucleus (see also side view in B), causing chromatin herniation and NE rupture. (inset) Sequence of events leading to NE rupture upon nuclear confinement, starting with formation of nuclear membrane blebs at nuclear lamina lesions that progress to chromatin hernias and NE rupture. (B) Side views of untreated cells (left) and cells in which actin organization/contractility or LINC complex function are disrupted (right). In normal cell culture conditions (top), actin or LINC complex disruption releases nuclear confinement and prevents NE rupture. When external confinement is applied through a compression device (bottom), cells exhibit NE rupture regardless of treatment. (C) Nuclear confinement during cell migration through tight openings, as encountered in extracellular matrix networks, extravasation, and interstitial spaces. (left) Perinuclear actomyosin network pushing the nucleus through the pore. (right) Arp 2/3-mediated actin polymerization supports the deformation of the nucleus through the pore. For simplicity, both processes are shown separately, even though they can likely appear in parallel in migrating cells.