Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
Integr Biol (Camb). 2021 Dec 15;13(10):246-257. doi: 10.1093/intbio/zyab017.
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.
肌动球蛋白细胞骨架使细胞能够抵抗变形、爬行、改变形状并感知周围环境。尽管已经研究了几十年，但分子成分如何组装成具有细胞观察到的力学特性的网络仍然知之甚少。最近，已经表明静止细胞的肌动球蛋白皮质可以经历频繁的、突然的重新配置和位移，称为细胞震动。值得注意的是，这种波动目前的肌动球蛋白网络物理模型没有预测到，其在细胞类型和力学环境中的普遍性以前也没有研究过。使用微孔阵列检测器，我们对细胞肌动球蛋白皮质和应力纤维网络的动态力学波动进行了高分辨率测量。这揭示了皮质动力学主要由细胞震动主导——位移呈胖尾分布的间歇性事件，有时跨越相隔 4 μm 的微孔，在所有研究的细胞类型中均如此。这些细胞包括 3T3 成纤维细胞，其中细胞震动在跨越组织相关范围 4.3 kPa-17 kPa 的基质硬度上持续存在，以及原代新生大鼠心肌成纤维细胞和肌成纤维细胞、人胚肾细胞和人骨肉瘤上皮（U2OS）细胞，在基质硬度相同的范围内观察到细胞震动。总体而言，这些发现表明皮质自我组织成一种边缘稳定的力学状态，其物理特性可能有助于细胞力学特性、活性行为和机械感觉。
