Author: Garg AA1, Jones TH1, Moss SM2, Mishra S3,4, Kaul K3,4, Ahirwar DK3,4, Ferree J1, Kumar P1, Subramaniam D5, Ganju RK3,4, Subramaniam VV6,7, Song JW8,9
Affiliation: <sup>1</sup>Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, 43210, USA.
<sup>2</sup>Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.
<sup>3</sup>Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
<sup>4</sup>Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
<sup>5</sup>College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
<sup>6</sup>Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, 43210, USA. subramaniam.1@osu.edu.
<sup>7</sup>Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. subramaniam.1@osu.edu.
<sup>8</sup>Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, 43210, USA. song.1069@osu.edu.
<sup>9</sup>Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA. song.1069@osu.edu.
Conference/Journal: Commun Biol.
Date published: 2019 Aug 8
Other:
Volume ID: 2 , Issue ID: 1 , Pages: 303 , Special Notes: doi: 10.1038/s42003-019-0550-z. , Word Count: 154
Interactions between cells and their environment influence key physiologic processes such as their propensity to migrate. However, directed migration controlled by extrinsically applied electrical signals is poorly understood. Using a novel microfluidic platform, we found that metastatic breast cancer cells sense and respond to the net direction of weak (∼100 µV cm-1), asymmetric, non-contact induced Electric Fields (iEFs). iEFs inhibited EGFR (Epidermal Growth Factor Receptor) activation, prevented formation of actin-rich filopodia, and hindered the motility of EGF-treated breast cancer cells. The directional effects of iEFs were nullified by inhibition of Akt phosphorylation. Moreover, iEFs in combination with Akt inhibitor reduced EGF-promoted motility below the level of untreated controls. These results represent a step towards isolating the coupling mechanism between cell motility and iEFs, provide valuable insights into how iEFs target multiple diverging cancer cell signaling mechanisms, and demonstrate that electrical signals are a fundamental regulator of cancer cell migration.
PMID: 31925108 DOI: 10.1038/s42003-019-0550-z