Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
Lab Chip. 2019 Apr 23;19(9):1579-1588. doi: 10.1039/c9lc00173e.
Collective cellular migration plays a central role in development, regeneration, and metastasis. In these processes, mechanical interactions between cells are fundamental but measurement of these interactions is often hampered by technical limitations. To overcome some of these limitations, here we describe a system that integrates microfluidics with traction microscopy (TM). Using this system we can measure simultaneously, and in real time, migration speeds, tractions, and intercellular tension throughout an island of confluent Madin-Darby canine kidney (MDCK) cells. The cell island is exposed to hepatocyte growth factor (HGF) at a controlled gradient of concentrations; HGF is known to elicit epithelial-to-mesenchymal transition (EMT) and cell scattering. As expected, the rate of expansion of the cell island was dependent on the concentration of HGF. Higher concentrations of HGF reduced intercellular tensions, as expected during EMT. A novel finding, however, is that the effects of HGF concentration and its gradient were seen within an island. This integrated experimental system thus provides an integrated tool to better understand cellular forces during collective cellular migration under chemical gradients.
细胞集体迁移在发育、再生和转移中起着核心作用。在这些过程中，细胞间的力学相互作用是基础，但这些相互作用的测量常常受到技术限制的阻碍。为了克服其中的一些限制，我们在这里描述了一个将微流控技术与牵引力显微镜（TM）集成的系统。使用该系统，我们可以实时、同时测量融合的 Madin-Darby 犬肾（MDCK）细胞岛中的迁移速度、牵引力和细胞间张力。该细胞岛被以受控浓度梯度的肝细胞生长因子（HGF）暴露；已知 HGF 引发上皮-间充质转化（EMT）和细胞散射。如预期的那样，细胞岛的扩展速度取决于 HGF 的浓度。更高浓度的 HGF 降低了细胞间的张力，这在 EMT 期间是预期的。然而，一个新的发现是，HGF 浓度及其梯度的影响在岛内可见。因此，这个集成的实验系统为在化学梯度下进行集体细胞迁移时更好地理解细胞力提供了一个集成的工具。
