集体细胞的运动受到细胞响应外部机械刺激的物理相互作用的变化的影响,包括流体流动。大多数组织在间质水平受到流体流动的影响,但是很少有研究研究了低流速对集体细胞的物理影响。在这项研究中,使用牵引微流体装置在静态或间质流(0、0.1和1μL/min)下研究了Madin-Darby犬肾(MDCK)上皮细胞的集体细胞迁移。细胞牵引力计算的优化首先通过改变来自荧光珠图像的询问窗口尺寸来实现。用700μm圆形图案的细胞聚集体的迁移分析表明,与静态条件相比,在缓慢流动(0.1和1μL/min)下的细胞通过降低细胞岛的大小和细胞速度而表现出抑制性迁移。细胞力的分析表明,与静态条件(〜50Pa)相比,慢流动条件(〜20Pa)下的牵引力水平较低。有趣的是,随着流速从0增加到1μL/min,细胞牵引力的标准偏差急剧下降,这表明流动会影响细胞群之间细胞牵引力的分布。在1μL/min的流体流速下,细胞的细胞张力增加了50%。钙阻滞剂的处理增加了流动条件下细胞的迁移速度,而细胞力几乎没有变化。总之,研究表明,间质流通过减少和重新分配细胞力抑制上皮细胞的集体运动。这些发现为研究间质流对细胞行为的影响提供了见解,如发展,再生,和形态发生。
The movement of collective cells is affected through changes in physical interactions of cells in response to external mechanical stimuli, including fluid flow. Most tissues are affected by fluid flow at the interstitial level, but few studies have investigated the physical effects in collective cells affected by a low flow rate. In this
study, collective cell migration of Madin-Darby canine kidney (MDCK) epithelial cells was investigated under static or interstitial flow (0, 0.1, and 1 μL/min) using a traction microfluidic device. The optimization of calculation of cellular traction forces was first achieved by changing interrogation window size from the fluorescent bead images. Migration analysis of cell collectives patterned with a 700 μm circular shape reveals that cells under the slow flow (0.1 and 1 μL/min) showed the inhibitory migration by decreasing cell island size and cellular speed compared to that of static condition. Analysis of cellular forces shows that level of traction forces was lower in the slow flow condition (~20 Pa) compared to that of static condition (~50 Pa). Interestingly, the standard deviation of traction force of cells was dramatically decreased as the flow rate increased from 0 to 1 μL/min, which indicates that flow affects the distribution of cellular traction forces among cell collectives. Cellular tension was increased by 50% in the cells under the fluid flow rate of 1 μL/min. Treatment of calcium blocker increased the migratory speed of cells under the flow condition, whereas there is little change of cellular forces. In conclusion, it has been shown that the interstitial flow inhibited the collective movement of epithelial cells by decreasing and re-distributing cellular forces. These findings provide insights into the
study of the effect of interstitial flow on cellular behavior, such as development, regeneration, and morphogenesis.