Pervasive cytoquakes in the actomyosin cortex across cell types and substrate stiffness

Pervasive cytoquakes in the actomyosin cortex across cell types and substrate stiffness
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DOI:
10.1093/intbio/zyab017
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发表时间:
2021-12-07
影响因子:
2.5
通讯作者:
Reich,Daniel H.
Reich,Daniel H.
中科院分区:
生物学4区
文献类型:
--
作者:
Shi,Yu;Sivarajan,Shankar;Reich,Daniel H.

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肌动蛋白细胞骨架使细胞能够抵抗变形、爬行、改变形状和感知周围环境。尽管经过了几十年的研究,但它的分子成分如何结合观察到的细胞机制形成网络,仍然知之甚少。最近,有研究表明,静止细胞的肌动球蛋白皮质可以经历频繁的、突然的重新配置和移位,称为细胞地震。值得注意的是,目前肌动球蛋白网络的物理模型不能预测这种波动,而且以前还没有研究过它们在细胞类型和机械环境中的流行度。利用微柱阵列探测器,我们对细胞肌球蛋白皮质和应力纤维网络的动态机械波动进行了高分辨率测量。这揭示了由细胞地震主导的皮质动力学-在所有研究的细胞类型中,间歇性事件具有厚尾分布的位移,有时跨越相隔4μm的微柱。这些细胞包括3T3成纤维细胞,其中细胞震动持续存在于与组织相关的4.3 kpa-17 kpa范围内的底物硬度上,以及原代新生大鼠心脏成纤维细胞和肌成纤维细胞、人胚胎肾细胞和人骨肉瘤上皮(U2OS)细胞,其中在相同硬度范围的底物上观察到细胞震动。总体而言,这些发现表明,大脑皮层自组织进入一种略微稳定的机械状态,这种状态的物理特性可能有助于细胞的机械特性、主动行为和机械感觉。
The actomyosin cytoskeleton enables cells to resist deformation, crawl, change their shape and sense their surroundings. Despite decades of study, how its molecular constituents can assemble together to form a network with the observed mechanics of cells remains poorly understood. Recently, it has been shown that the actomyosin cortex of quiescent cells can undergo frequent, abrupt reconfigurations and displacements, called cytoquakes. Notably, such fluctuations are not predicted by current physical models of actomyosin networks, and their prevalence across cell types and mechanical environments has not previously been studied. Using micropost array detectors, we have performed high-resolution measurements of the dynamic mechanical fluctuations of cells’ actomyosin cortex and stress fiber networks. This reveals cortical dynamics dominated by cytoquakes—intermittent events with a fat-tailed distribution of displacements, sometimes spanning microposts separated by 4 μm, in all cell types studied. These included 3T3 fibroblasts, where cytoquakes persisted over substrate stiffnesses spanning the tissue-relevant range of 4.3 kPa–17 kPa, and primary neonatal rat cardiac fibroblasts and myofibroblasts, human embryonic kidney cells and human bone osteosarcoma epithelial (U2OS) cells, where cytoquakes were observed on substrates in the same stiffness range. Overall, these findings suggest that the cortex self-organizes into a marginally stable mechanical state whose physics may contribute to cell mechanical properties, active behavior and mechanosensing.