Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization.

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization.
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肌动球蛋白和波形蛋白细胞骨架网络调节核形状、力学和染色质组织。

DOI:
10.1038/s41598-017-05467-x
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发表时间:
2017-07-12
期刊:
影响因子:
4.6
通讯作者:
Gavara N
Gavara N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Keeling MC;Flores LR;Dodhy AH;Murray ER;Gavara N

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细胞骨架对细胞核状态的调节是细胞功能的重要组成部分。肌动球蛋白应力纤维,微管和中间丝在整合细胞核到其环境中,并影响其机械状态有不同的和互补的作用。然而,细胞骨架网络的相互联系使得很难剖析它们对细胞核的个体影响。我们使用简单的图像分析方法来表征核状态,估计核体积,泊松比,表观弹性模量和染色质凝聚。通过将它们与细胞骨架定量相结合,我们评估了细胞骨架组织如何调节核状态。我们报告了一些细胞类型的细胞核显示拉胀特性。此外,应力纤维和中间丝调节细胞核的机械性质以及染色质凝聚。相反,核体积和其总体形态是由肌球蛋白施加的细胞内向外拉力调节的。细胞骨架对细胞核施加的调节导致的变化与细胞核内在改变时观察到的变化幅度相似,诱导染色质去浓缩或细胞分化。我们的方法可以精确定位不同的细胞骨架蛋白在生理和病理条件下对核机械状态的贡献,进一步加深我们对细胞行为的一个关键方面的理解。
The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus. We use simple image analysis approaches to characterize nuclear state, estimating nuclear volume, Poisson’s ratio, apparent elastic modulus and chromatin condensation. By combining them with cytoskeletal quantification, we assess how cytoskeletal organization regulates nuclear state. We report for a number of cell types that nuclei display auxetic properties. Furthermore, stress fibres and intermediate filaments modulate the mechanical properties of the nucleus and also chromatin condensation. Conversely, nuclear volume and its gross morphology are regulated by intracellular outward pulling forces exerted by myosin. The modulation exerted by the cytoskeleton onto the nucleus results in changes that are of similar magnitude to those observed when the nucleus is altered intrinsically, inducing chromatin decondensation or cell differentiation. Our approach allows pinpointing the contribution of distinct cytoskeletal proteins to nuclear mechanical state in physio- and pathological conditions, furthering our understanding of a key aspect of cellular behaviour.
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