Intrinsic cell rheology drives junction maturation.

Intrinsic cell rheology drives junction maturation.
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DOI:
10.1038/s41467-022-32102-9
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发表时间:
2022-08-17
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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高等真核生物进化成功的一个基本特性是稳定的细胞间凝聚力。然而,如何内在的细胞流变学和刚度有助于连接稳定和成熟知之甚少。我们证明,局部调制的细胞流变学管理的过渡松弛,起伏的细胞-细胞接触(弱粘附)到一个成熟的,直的交界处(最佳粘附)。限制在不同几何形状上的细胞对具有异质弹性图,并且协调地控制它们自己的内在流变学。更顺应细胞对生长在圆松弛接触,而刚性三角形细胞对有利于直路口侧翼收缩薄束。与直觉相反,更直的细胞-细胞接触具有降低的受体密度和更少的动态连接肌动蛋白,这表明不寻常的适应性机械响应以稳定细胞-细胞粘附。我们的建模通知松弛的连接产生的圆形细胞对的失败,以增加自己的内在刚度和抵抗来自相邻细胞的压力。不能形成直的接合部可以通过在较硬的基板上人为地增加机械应力来逆转。我们的数据通知最小的内在流变学,以产生一个成熟的交界处,并提供一个跳板,对理解元素管理组织水平的力学。固有的细胞特性如刚度如何有助于细胞-细胞连接的稳定性还没有很好的描述。在这里,他们表明邻近细胞的皮质、细胞骨架和细胞核中更高水平的内在细胞力学促进了交界处的成熟。
A fundamental property of higher eukaryotes that underpins their evolutionary success is stable cell-cell cohesion. Yet, how intrinsic cell rheology and stiffness contributes to junction stabilization and maturation is poorly understood. We demonstrate that localized modulation of cell rheology governs the transition of a slack, undulated cell-cell contact (weak adhesion) to a mature, straight junction (optimal adhesion). Cell pairs confined on different geometries have heterogeneous elasticity maps and control their own intrinsic rheology co-ordinately. More compliant cell pairs grown on circles have slack contacts, while stiffer triangular cell pairs favour straight junctions with flanking contractile thin bundles. Counter-intuitively, straighter cell-cell contacts have reduced receptor density and less dynamic junctional actin, suggesting an unusual adaptive mechano-response to stabilize cell-cell adhesion. Our modelling informs that slack junctions arise from failure of circular cell pairs to increase their own intrinsic stiffness and resist the pressures from the neighbouring cell. The inability to form a straight junction can be reversed by increasing mechanical stress artificially on stiffer substrates. Our data inform on the minimal intrinsic rheology to generate a mature junction and provide a springboard towards understanding elements governing tissue-level mechanics. How intrinsic cell properties such as stiffness contribute to cell-cell junction stabilization is not well described. Here they show that higher levels of intrinsic cell mechanics at the cortex, cytoskeleton and nucleus of neighboring cells promote junctional maturation.
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