Mechanotactic activation of TGF‐β by PEDOT artificial microenvironments triggers epithelial to mesenchymal transition

Dhawan, U. , Wang, W.‐L., Gautam, B., Aerathupalathu Janardhanan, J., Hsiao, P.‐C., Tu, H.‐L. and Yu, H.‐H. (2020) Mechanotactic activation of TGF‐β by PEDOT artificial microenvironments triggers epithelial to mesenchymal transition. Advanced Biosystems, 4(2), 1900165. (doi: 10.1002/adbi.201900165) (PMID:32293138)

Abstract

pithelial to mesenchymal transition (EMT) is integral for cells to acquire metastatic properties, and ample evidence links it to bioorganic framework of the tumor microenvironment (TME). Hydroxymethyl-functionalized 3,4-ethylenedioxythiophene polymer (PEDOT-OH) enables construction of diverse nanotopography size and morphologies and is therefore exploited to engineer organic artificial microenvironments bearing nanodots from 300 to 1000 nm in diameter to understand spatiotemporal EMT regulation by biophysical components of the TME. MCF-7 breast cancer cells are cultured on these artificial microenvironments, and temporal regulation of cellular morphology and EMT markers is investigated. The results show that upon physical stimulation, cells on 300 nm artificial microenvironments advance to EMT and display a decreased extracellular matrix (ECM) protein secretion. In contrast, cells on 500 nm artificial microenvironments are trapped in EMT-imbalance. Interestingly, cells on 1000 nm artificial microenvironments resemble those on control surfaces. Upon further investigation, it is found that EMT induction is triggered via transforming growth factor β (TGF-β) and ECM cleaving protein, matrix metalloproteinease-9. Immunostaining EMT proteins highlighted that EMT induction is achieved through attenuation of cell–cell and cell–microenvironment adhesions. The physical stimulation-induced TGF-β perturbation can have a profound impact on the understanding of tumor-promoting signaling cascades originated by cellular microenvironment.

• Item Type: Articles
• Additional Information: This study was supported by the Ministry of Science and Technology (MOST) of Taiwan (MOST-106-2028-M-001-MY3, MOST-107-2627-M-001-007 and MOST 107-2113-M-001-032-MY3). This project was also supported by Academia Sinica Thematic Project (AS-TP-107-ML09).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dhawan, Dr Udesh
• Authors: Dhawan, U., Wang, W.‐L., Gautam, B., Aerathupalathu Janardhanan, J., Hsiao, P.‐C., Tu, H.‐L., and Yu, H.‐H.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Advanced Biosystems
• Publisher: Wiley
• ISSN: 2366-7478
• Published Online: 01 January 2020