Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity

Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity
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具有细胞尺度刚度异质性的基质上双 durotaxing 细胞的核激活

DOI:
10.1101/2021.10.30.466554
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发表时间:
2021
期刊:
bioRxiv
影响因子:
--
通讯作者:
Tanaka Kazusa
Tanaka Kazusa
中科院分区:
--
文献类型:
--
作者:
Kidoaki Satoru;Ebata Hiroyuki;Moriyama Kosuke;Kuboki Thasaneeya;Tsuji Yukie;Sawada Rumi;Sasaki Saori;Okuda Tatsuya;Hamano Kosuke;Kawano Takahito;Yamamoto Aki;Kono Ken;Tanaka Kazusa

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生物体通常由具有微观细胞尺度刚度-非均质性的各种组织组成,其中一些细胞在长期运动过程中受到来自异质细胞外环境的动态波动的机械刺激。虽然细胞内应力动力学(ISD)与细胞功能(如增殖和分化)的调节密切相关,可以在细胞在具有刚度异质性的基质上迁移时进行特征性调节,但ISD的波动模式如何影响细胞功能尚不清楚。在本研究中,我们证明了间充质干细胞(MSCs)在具有刚性三角形结构域的微弹性图案凝胶上的双重硬移(即正向和反向硬移)显著放大了ISD、核形状和染色质空间分布的波动,使细胞远离张力平衡。我们提供的证据表明,在双时间消耗的间充质干细胞中,染色质波动的放大可以引起细胞活力的激活和干性的维持。
Living organisms are typically composed of various tissues with microscopic cell-scale stiffness-heterogeneity, in which some cells receive dynamically fluctuating mechanical stimuli from the heterogeneous extracellular milieu during long-term movement. Although intracellular stress dynamics (ISD), which are closely related to the regulation of cell functions such as proliferation and differentiation, can be characteristically modulated in cells migrating on a matrix with stiffness-heterogeneity, it has been unclear how the mode of fluctuation of ISD affects cell functions. In the present study, we demonstrate that mesenchymal stem cells (MSCs) dual-durotaxing (i.e., both forward and reverse durotaxis) on microelastically-patterned gels with stiff triangular domains markedly amplify the fluctuation of ISD, nuclear shape, and the spatial distribution of chromatins, which makes the cells remain far from tensional equilibrium. We provide evidence that amplified chromatin fluctuation in the dual-durotaxing MSCs can cause activation of cellular vigor and maintenance of the stemness.
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