Local, transient tensile stress on the nuclear membrane causes membrane rupture
Local, transient tensile stress on the nuclear membrane causes membrane rupture
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核膜上的局部瞬时拉伸应力导致膜破裂
DOI：
10.1091/mbc.e18-09-0604
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发表时间：
2019
影响因子：
3.3
通讯作者：
Weaver, Valerie Marie
中科院分区：
文献类型：
--
作者：
Zhang, Qiao;Tamashunas, Andrew C.;Agrawal, Ashutosh;Torbati, Mehdi;Katiyar, Aditya;Dickinson, Richard B.;Lammerding, Jan;Lele, Tanmay P.;Weaver, Valerie Marie
癌细胞在狭窄的狭窄中迁移会在细胞核上产生压应力，使其变形并导致核膜破裂。核膜破裂使核内含物和细胞质内容物之间不受控制地交换。局部张应力也可引起核变形，但这种变形是否伴随核膜破裂尚不清楚。在这里，我们使用了直接力探头，通过在核膜上施加瞬时张应力来使核局部变形。我们发现，正常乳腺上皮细胞(∼-10A细胞)的瞬间(∼0.2 S)形变(MCF1%投影面应变)足以导致核膜破裂。核膜破裂程度与核变形的大小和外加拉应力的大小有关。核探针在野生型和缺失层粘连蛋白缺失的MCF-10A细胞中的扩散通量比较表明，层粘连蛋白A/C而不是层粘连蛋白B2保护核膜免受拉伸应力的破坏。我们的结果表明，通常由局部张应力引起的瞬时核变形足以导致核膜破裂。
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 (∼0.2 s) deformation (∼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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影响因子：
64.8
作者：
通讯作者：
--
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
DOI：
10.1073/pnas.94.3.849
发表时间：
1997-02-04
影响因子：
11.1
作者：
Maniotis, AJ;Chen, CS;Ingber, DE
通讯作者：
Ingber, DE
DOI：
10.1039/c5ib00200a
发表时间：
2015-12
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Davidson PM;Sliz J;Isermann P;Denais C;Lammerding J
通讯作者：
Lammerding J