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Gaussian curvature dilutes the nuclear lamina favoring nuclear rupture especially at high strain rate

機(jī)譯：高斯曲率稀釋了核層有利于核破裂尤其是在高應(yīng)變速率下

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Nuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B filaments stably interact with the nuclear membrane at sites of low Gaussian curvature yet dilute at high curvature to favor rupture, whereas lamin-A depletion requires high strain-rates. Live-cell imaging of lamin-B1 gene-edited cancer cells is complemented by fixed-cell imaging of rupture in: iPS-derived progeria patients cells, cells within beating chick embryo hearts, and cancer cells with multi-site rupture after migration through small pores. Data fit a model of stiff filaments that detach from a curved surface.Rupture is modestly suppressed by inhibiting myosin-II and by hypotonic stress, which slow the strain-rates. Lamin-A dilution and rupture probability indeed increase above a threshold rate of nuclear pulling. Curvature-sensing mechanisms of proteins at plasma membranes, including Piezo1, might thus apply at nuclear membranes.Summary statement: High nuclear curvature drives lamina dilution and nuclear envelope rupture even when myosin stress is inhibited. Stiff filaments generally dilute from sites of high Gaussian curvature, providing mathematical fits of experiments.
機(jī)譯：長期以來，核破裂一直與核纖層蛋白的缺陷或缺陷有關(guān)，最近的結(jié)果也表明肌動(dòng)球蛋白應(yīng)激的作用，但破裂的關(guān)鍵物理決定因素仍不清楚。在這里，層粘連 B 絲在低高斯曲率位點(diǎn)與核膜穩(wěn)定相互作用，但在高曲率處稀釋以促進(jìn)破裂，而層粘連 A 耗竭需要高應(yīng)變速率。lamin-B1基因編輯的癌細(xì)胞的活細(xì)胞成像與以下破裂的固定細(xì)胞成像相輔相成：iPS衍生的早衰患者細(xì)胞，跳動(dòng)的雞胚心臟內(nèi)的細(xì)胞以及通過小孔遷移后具有多位點(diǎn)破裂的癌細(xì)胞。數(shù)據(jù)擬合從曲面分離的剛性細(xì)絲模型。通過抑制肌球蛋白 II 和低滲應(yīng)激適度抑制破裂，從而減慢應(yīng)變率。Lamin-A 稀釋和破裂概率確實(shí)增加到核拉動(dòng)閾值速率以上。因此，質(zhì)膜上蛋白質(zhì)的曲率感應(yīng)機(jī)制，包括 Piezo1，可能適用于核膜?？偨Y(jié)陳述：即使肌球蛋白應(yīng)激受到抑制，高核曲率也會(huì)驅(qū)動(dòng)椎板稀釋和核膜破裂。堅(jiān)硬的細(xì)絲通常從高斯曲率位點(diǎn)稀釋，提供數(shù)學(xué)擬合實(shí)驗(yàn)。

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