Schneider David, Baronsky Thilo, Pietuch Anna, Rother Jan, Oelkers Marieelen, Fichtner Dagmar, Wedlich Doris, Janshoff Andreas
Institute of Physical Chemistry, Georg-August-University Göttingen, Göttingen, Germany.
PLoS One. 2013 Dec 5;8(12):e80068. doi: 10.1371/journal.pone.0080068. eCollection 2013.
Structural alterations during epithelial-to-mesenchymal transition (EMT) pose a substantial challenge to the mechanical response of cells and are supposed to be key parameters for an increased malignancy during metastasis. Herein, we report that during EMT, apical tension of the epithelial cell line NMuMG is controlled by cell-cell contacts and the architecture of the underlying actin structures reflecting the mechanistic interplay between cellular structure and mechanics. Using force spectroscopy we find that tension in NMuMG cells slightly increases 24 h after EMT induction, whereas upon reaching the final mesenchymal-like state characterized by a complete loss of intercellular junctions and a concerted down-regulation of the adherens junction protein E-cadherin, the overall tension becomes similar to that of solitary adherent cells and fibroblasts. Interestingly, the contribution of the actin cytoskeleton on apical tension increases significantly upon EMT induction, most likely due to the formation of stable and highly contractile stress fibers which dominate the elastic properties of the cells after the transition. The structural alterations lead to the formation of single, highly motile cells rendering apical tension a good indicator for the cellular state during phenotype switching. In summary, our study paves the way towards a more profound understanding of cellular mechanics governing fundamental morphological programs such as the EMT.
上皮-间质转化(EMT)过程中的结构改变对细胞的力学响应构成了重大挑战,并且被认为是转移过程中恶性程度增加的关键参数。在此,我们报告在EMT过程中,上皮细胞系NMuMG的顶端张力由细胞间接触以及反映细胞结构与力学之间机制相互作用的底层肌动蛋白结构的架构所控制。使用力谱技术,我们发现EMT诱导24小时后,NMuMG细胞中的张力略有增加,而当达到以细胞间连接完全丧失和黏附连接蛋白E-钙黏蛋白协同下调为特征的最终间充质样状态时,整体张力变得与单独贴壁细胞和成纤维细胞的张力相似。有趣的是,EMT诱导后,肌动蛋白细胞骨架对顶端张力的贡献显著增加,这很可能是由于形成了稳定且高度收缩的应力纤维,这些应力纤维在转变后主导了细胞的弹性特性。结构改变导致形成单个高迁移性细胞,使顶端张力成为表型转换期间细胞状态的良好指标。总之,我们的研究为更深入理解控制诸如EMT等基本形态程序的细胞力学铺平了道路。