BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland.
Sci Rep. 2021 Sep 16;11(1):18520. doi: 10.1038/s41598-021-97900-5.
Cellular forces, mechanics and other physical factors are important co-regulators of normal cell and tissue physiology. These cues are often misregulated in diseases such as cancer, where altered tissue mechanics contribute to the disease progression. Furthermore, intercellular tensile and compressive force-related signaling is highlighted in collective cell behavior during development. However, the mechanistic understanding on the role of physical forces in regulation of cellular physiology, including gene expression and signaling, is still lacking. This is partly because studies on the molecular mechanisms of force transmission require easily controllable experimental designs. These approaches should enable both easy mechanical manipulation of cells and, importantly, readouts ranging from microscopy imaging to biochemical assays. To achieve a robust solution for mechanical manipulation of cells, we developed devices built of LEGO bricks allowing manual, motorized and/or cyclic cell stretching and compression studies. By using these devices, we show that [Formula: see text]-catenin responds differentially to epithelial monolayer stretching and lateral compression, either localizing more to the cell nuclei or cell-cell junctions, respectively. In addition, we show that epithelial compression drives cytoplasmic retention and phosphorylation of transcription coregulator YAP1. We provide a complete part listing and video assembly instructions, allowing other researchers to build and use the devices in cellular mechanics-related studies.
细胞力、力学和其他物理因素是正常细胞和组织生理学的重要共同调节剂。这些线索在癌症等疾病中经常失调,在癌症中,组织力学的改变有助于疾病的进展。此外,在发育过程中的细胞集体行为中,细胞间张力和压缩力相关信号也很突出。然而,对于物理力在调节细胞生理学(包括基因表达和信号转导)中的作用的机制理解仍然缺乏。这在一定程度上是因为力传递的分子机制研究需要易于控制的实验设计。这些方法应该既能够轻松地对细胞进行机械操作,又能够进行从显微镜成像到生化分析的各种检测。为了实现对细胞的机械操作的稳健解决方案,我们开发了由乐高积木制成的设备,允许手动、电动和/或周期性的细胞拉伸和压缩研究。通过使用这些设备,我们表明 [Formula: see text]-连环蛋白对上皮单层拉伸和侧向压缩的反应不同,分别更多地定位于细胞核或细胞-细胞连接处。此外,我们表明上皮细胞的压缩会导致细胞质中 YAP1 的保留和磷酸化。我们提供了完整的零件清单和视频组装说明,允许其他研究人员在与细胞力学相关的研究中构建和使用这些设备。