Nuclear blebs are rupture‑prone plastic deformations

Abnormal nuclear morphology is a hallmark of various human diseases. Nuclear blebs are herniations of the nucleus found in many diseased nuclei and often cause nuclear rupture. While nuclear blebbing and rupture are known to cause dysfunction, the relationship between nuclear blebbing and rupture, longevity, and plasticity remain unclear. We performed time-lapse imaging of nuclear localization signal green fluorescent protein (NLS–GFP) to track the history of individual blebbing events. Nuclear blebs typically form within 12 hours after the cell exits mitosis. We find that nuclear blebs predominantly form first, leading to multiple nuclear ruptures. Nuclear blebs are either long-lived, with many requiring entry into mitosis for reabsorption, or short-lived largely due to being the second bleb on a nucleus. Nuclear blebs remain upon both in-cell actin depolymerization and nuclear isolation through micromanipulation. We reveal that nuclear blebs are plastic deformations that provide a persistent site of nuclear rupture.