Mechanically induced pre-mitotic nuclear deformations promote nuclear rupture through lamin B1 depletion

Abstract

Disassembly of the nuclear lamina is essential for successful mitosis in eukaryotic cells, but the mechanism that triggers the lamina breakdown remains unclear. Using 3D fluorescence microscopy imaging combined with 3D curvature analysis, we found that microtubule-dependent invaginations trigger lamina remodelling and lamin B1 network disruption. Monte Carlo simulations provide mechanistic insight into how those invaginations induce a mechanical discontinuity between isotropic expansion and anisotropic shrinking forces at the rim of the nucleus, which correlated with lamin B1 depletion sites and the location of cytoplasmic protein influx within the nucleus. Our findings suggest that pre-mitotic modifications of the lamina function as a mechanical trigger to facilitate nuclear rupture and are thereby a key driver of mitotic entry, complementing established biochemical pathways.