Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany; Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany; Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
Biophys J. 2021 Aug 17;120(16):3516-3526. doi: 10.1016/j.bpj.2021.05.006. Epub 2021 May 20.
The actin cortex is a key structure for cellular mechanics and cellular migration. Accordingly, cancer cells were shown to change their actin cytoskeleton and their mechanical properties in correlation with different degrees of malignancy and metastatic potential. Epithelial-mesenchymal transition (EMT) is a cellular transformation associated with cancer progression and malignancy. To date, a detailed study of the effects of EMT on the frequency-dependent viscoelastic mechanics of the actin cortex is still lacking. In this work, we have used an established atomic force microscope-based method of cell confinement to quantify the rheology of the actin cortex of human breast, lung, and prostate epithelial cells before and after EMT in a frequency range of 0.02-2 Hz. Interestingly, we find for all cell lines opposite EMT-induced changes in interphase and mitosis; whereas the actin cortex softens upon EMT in interphase, the cortex stiffens in mitosis. Our rheological data can be accounted for by a rheological model with a characteristic timescale of slowest relaxation. In conclusion, our study discloses a consistent rheological trend induced by EMT in human cells of diverse tissue origin, reflecting major structural changes of the actin cytoskeleton upon EMT.
肌动蛋白皮质是细胞力学和细胞迁移的关键结构。因此，研究表明，癌细胞会改变其肌动蛋白细胞骨架，并与其恶性程度和转移潜能的不同程度相关的机械性能。上皮-间充质转化（EMT）是与癌症进展和恶性有关的细胞转化。迄今为止，关于 EMT 对肌动蛋白皮质的频率相关粘弹性力学的影响的详细研究仍然缺乏。在这项工作中，我们使用了一种已建立的基于原子力显微镜的细胞限制方法，在 0.02-2 Hz 的频率范围内定量测量了人类乳腺、肺和前列腺上皮细胞 EMT 前后肌动蛋白皮质的流变特性。有趣的是，我们发现所有细胞系的 EMT 诱导的间期和有丝分裂的变化相反；尽管在间期肌动蛋白皮质在 EMT 后变软，但在有丝分裂中皮质变硬。我们的流变数据可以用具有最慢弛豫特征时间尺度的流变模型来解释。总之，我们的研究揭示了 EMT 在不同组织来源的人类细胞中诱导的一致流变趋势，反映了 EMT 后肌动蛋白细胞骨架的主要结构变化。
