Introduction

The mechanical response of large multi-cellular collectives to external stretch has remained largely unexplored, despite its relevance to normal function and to external challenges faced by some tissues. Here, we introduced a simple hybrid silicone substrate to enable external stretch while providing a physiologically relevant physical micro-environment for cells.

Methods

We micropatterned epithelial islands on the substrate using a stencil to allow for a circular island shape without restraining island edges. We then used traction force microscopy to determine the strain energy and the inter-cellular sheet tension within the island as a function of time after stretch.

Results

While the strain energy stored in the substrate for unstretched cell islands stayed constant over time, a uniaxial 10% stretch resulted in an abrupt increase, followed by sustained increase in the strain energy of the islands over tens of minutes, indicating slower dynamics than for single cells reported previously. The sheet tension at the island mid-line perpendicular to the stretch direction also more than doubled compared to unstretched islands. Interestingly, the sheet tension at the island mid-line parallel to the stretch direction also reached similar levels over tens of minutes indicating the tendency of the island to homogenize its internal stress.

Conclusions

We found that the sheet tension within large epithelial islands depends on the midline direction relative to that of the stretch initially, but not at longer times. We suggest that the hybrid silicone substrate provides an accessible substrate for studying the mechanobiology of large epithelial cell islands.

中文翻译：

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上皮岛在混合有机硅基底上进行单轴拉伸的机械响应。

介绍

大型多细胞集体对外部拉伸的机械反应在很大程度上仍未得到探索，尽管它与正常功能和某些组织面临的外部挑战有关。在这里，我们引入了一种简单的混合有机硅基板，以实现外部拉伸，同时为细胞提供生理相关的物理微环境。

方法

我们使用模板在基板上对上皮岛进行微图案化，以允许在不限制岛边缘的情况下形成圆形岛形状。然后，我们使用牵引力显微镜来确定岛内的应变能和细胞间片张力作为拉伸后时间的函数。

结果

虽然存储在基板中的未拉伸细胞岛的应变能随时间保持恒定，但单轴拉伸 10% 会导致突然增加，随后岛的应变能在数十分钟内持续增加，表明动力学比单轴拉伸慢细胞先前报道。与未拉伸的岛相比，垂直于拉伸方向的岛中线处的片材张力也增加了一倍以上。有趣的是，平行于拉伸方向的岛中线处的片材张力在数十分钟内也达到了相似的水平，表明岛的内应力趋于均匀。

结论

我们发现大上皮岛内的片张力取决于中线方向相对于最初的拉伸方向，但不是在更长的时间。我们建议混合有机硅基底为研究大上皮细胞岛的机械生物学提供了一种可接近的基底。