期刊
MOLECULAR BIOLOGY OF THE CELL
卷 30, 期 7, 页码 899-906出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E18-09-0604
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资金
- National Institutes of Health [R01 EB014869, R01 HL082792, U54 CA210184]
- Department of Defense Breast Cancer Research Program (Breakthrough Award) [BC150580]
- National Science Foundation
Cancer cell migration through narrow constrictions generates compressive stresses on the nucleus that deform it and cause rupture of nuclear membranes. Nuclear membrane rupture allows uncontrolled exchange between nuclear and cytoplasmic contents. Local tensile stresses can also cause nuclear deformations, but whether such deformations are accompanied by nuclear membrane rupture is unknown. Here we used a direct force probe to locally deform the nucleus by applying a transient tensile stress to the nuclear membrane. We found that a transient (similar to 0.2 s) deformation (similar to 1% projected area strain) in normal mammary epithelial cells (MCF-10A cells) was sufficient to cause rupture of the nuclear membrane. Nuclear membrane rupture scaled with the magnitude of nuclear deformation and the magnitude of applied tensile stress. Comparison of diffusive fluxes of nuclear probes between wild-type and lamin-depleted MCF-10A cells revealed that lamin A/C, but not lamin B2, protects the nuclear membranes against rupture from tensile stress. Our results suggest that transient nuclear deformations typically caused by local tensile stresses are sufficient to cause nuclear membrane rupture.
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