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Metabolically intact nuclei are fluidized by the activity of the chromatin remodeling motor BRG1
Biophysical Journal ( IF 3.2 ) Pub Date : 2024-11-30 , DOI: 10.1016/j.bpj.2024.11.3322
Fitzroy J. Byfield, Behnaz Eftekhari, Kaeli Kaymak-Loveless, Kalpana Mandal, David Li, Rebecca G. Wells, Wenjun Chen, Jasna Brujic, Guilia Bergamaschi, Gijs J.L. Wuite, Alison E. Patteson, Paul A. Janmey

The structure and dynamics of the cell nucleus regulate nearly every facet of the cell, and changes in nuclear shape can limit cell motility. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization that is driven by the BRG1 motor of the SWI/SNF/BAF chromatin remodeling complex. Atomic force microscopy measurements show that the nucleus alters stiffness in response to the cell substrate stiffness, which is retained after the nucleus is isolated, and that the work of nuclear compression is mostly dissipated rather than elastically stored. Inhibiting BRG1 stiffens the nucleus and eliminates dissipation and nuclear remodeling both in isolated nuclei and in intact cells. These findings demonstrate a novel link between nuclear motor activity and global nuclear mechanics.

中文翻译:


代谢完整的细胞核通过染色质重塑马达 BRG1 的活动而流化



细胞核的结构和动力学几乎调节着细胞的每一个方面,细胞核形状的变化会限制细胞的运动。虽然细胞核通常被视为细胞中最坚硬的细胞器,但细胞仍然可以通过小的机械应力使细胞核变形为大应变。在这里,我们表明细胞核的机械反应表现出由 SWI/SNF/BAF 染色质重塑复合物的 BRG1 电机驱动的主动流化。原子力显微镜测量表明,细胞核的刚度会随着细胞基质的刚度而改变,而细胞核的刚度在细胞核被分离后仍然存在,并且核压缩的工作大部分是消散的,而不是弹性储存的。抑制 BRG1 可使细胞核变硬,并消除离体细胞核和完整细胞中的耗散和细胞核重塑。这些发现证明了核运动活动与全球核力学之间存在新的联系。
更新日期:2024-11-30
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