Institute of Physiology II, University of Münster, Germany.
Nanotechnology. 2010 Jul 2;21(26):265102. doi: 10.1088/0957-4484/21/26/265102. Epub 2010 Jun 4.
Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-beta1. TGF-beta1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-beta1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-beta1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.
炎症和细胞纤维化通常意味着细胞因子 TGF-β1 的参与。TGF-β1 诱导上皮细胞-间充质转化（EMT），这一术语描述了上皮细胞特异性功能的丧失。这个过程的一个指示是细胞形状沿应力纤维形成而拉长。已经发现了 TGF-β1 的许多信号通路，但机械方面尚未得到研究。在这项研究中，原子力显微镜（AFM）用于分析近端肾小管上皮细胞（NRK52E）中的 EMT 的表面形貌和机械特性。观察到伸长细胞、应力纤维形成增加以及微绒毛相容结构的丧失，这些都是 EMT 的特征性标志。此外，在 TGF-β1 刺激六天后，AFM 可以识别出刚度增加了 71%。作为一种新的形貌现象，在细胞-细胞连接处出现了结节状突起。它们优先出现在应力纤维穿过边界的部位。由于这些结节状突起对产生力的抑制剂敏感，因此它们可以指示细胞内张力。结果表明，升高的张力对细胞形貌有明显的影响。
