Dynamics of TGF-β Induced Epithelial-To-Mesenchymal Transition Monitored by Electric Cell-Substrate Impedance Sensing

Biochim Biophys Acta. 2011 Dec;1813(12):2099-107. doi: 10.1016/j.bbamcr.2011.07.016. Epub 2011 Jul 31.


The epithelial-to-mesenchymal transition (EMT) is a program of cellular development associated with loss of cell-cell contacts, a decreased cell adhesion and substantial morphological changes. Besides its importance for numerous developmental processes, EMT has also been held responsible for the development and progression of tumors and formation of metastases. The influence of the cytokine transforming growth factor β1 (TGF-β1) induced EMT on structure, migration, cytoskeletal dynamics and long-term correlations of the mammalian epithelial cell lines NMuMG, A549 and MDA-MB231 was investigated with time-resolved impedance analysis. The three cell lines show important differences in concentration dependency, cellular morphology and dynamics upon their response to TGF-β1. A549 cells and the non-tumor mouse epithelial cell line NMuMG show a substantial change in morphology mirrored in stepwise changes of their phenotype upon cytokine treatment. Impedance based measurements of micromotility reveal a complex dynamic response to TGF-β1 exposure which leads to a transient increase in fluctuation amplitude and long-term correlation. These changes in fluctuation amplitude are also detectable for MDA-MB231 cells, whereas the long-term correlation remains unvaried. We were able to distinguish three time domains during EMT. Initially, all cell lines display an increase in micromotion lasting 4 to 9h termed transitional state I. This regime is followed by transitional state II lasting approximately 20 h, where cellular dynamics are diminished and, in case of the NMuMG cell line, a loss of cell-cell contacts occurs. Finally, the transformation into the mesenchymal-like phenotype occurs 24-30 h after exposure to TGF-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosensing Techniques*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Differentiation
  • Cells, Cultured
  • Electric Impedance*
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Transforming Growth Factor beta / pharmacology*


  • Transforming Growth Factor beta