Nuclear fragility, blaming the blebs

Although textbook pictures depict the cell nucleus as a simple ovoid object, it is now clear that it adopts a large variety of shapes in tissues. When cells deform, because of cell crowding or migration through dense matrices, the nucleus is subjected to large constraints that alter its shape. In this review, we discuss recent studies related to nuclear fragility, focusing on the surprising finding that the nuclear envelope can form blebs. Contrary to the better-known plasma membrane blebs, nuclear blebs are unstable and almost systematically lead to nuclear envelope opening and uncontrolled nucleocytoplasmic mixing. They expand, burst, and repair repeatedly when the nucleus is strongly deformed. Although blebs are a major source of nuclear instability, they are poorly understood so far, which calls for more in-depth studies of these structures.