@article{3913079dd9c841f48612700dd02de997,
title = "Electrically synchronizing and modulating the dynamics of ERK activation to regulate cell fate",
abstract = "Intracellular signaling dynamics play fundamental roles in cell biology. Precise modulation of the amplitude, duration, and frequency of signaling activation will be a powerful approach to investigate molecular mechanisms as well as to engineer signaling to control cell behaviors. Here, we showed a practical approach to achieve precise amplitude modulation (AM), frequency modulation (FM), and duration modulation (DM) of MAP kinase activation. Alternating current (AC) electrical stimulation induced synchronized ERK activation. Amplitude and duration of ERK activation were controlled by varying stimulation strength and duration. ERK activation frequencies were arbitrarily modulated with trains of short AC applications with accurately defined intervals. Significantly, ERK dynamics coded by well-designed AC can rewire PC12 cell fate independent of growth factors. This technique can be used to synchronize and modulate ERK activation dynamics, thus would offer a practical way to control cell behaviors in vivo without the use of biochemical agents or genetic manipulation.",
keywords = "Biotechnology, Cell biology, Functional aspects of cell biology, Integrative aspects of cell biology",
author = "Liang Guo and Kan Zhu and Michael Pargett and Adam Contreras and Patrick Tsai and Quan Qing and Wolfgang Losert and John Albeck and Min Zhao",
note = "Funding Information: This work is supported by the AFOSR- MURI grant FA9550-16-1-0052 , and NIH 1R01EY019101 . Work in Zhao Laboratory is also supported by NEI Core Grant ( P-30 EY012576 , PI. Jack Werner), the Research to Prevent Blindness, Inc. JA is supported by NIH R01GM115650 . The authors would like to thank Heather Blizard from the Albeck lab for assistance on electrotransfection. Funding Information: This work is supported by the AFOSR-MURI grant FA9550-16-1-0052, and NIH 1R01EY019101. Work in Zhao Laboratory is also supported by NEI Core Grant (P-30 EY012576, PI. Jack Werner), the Research to Prevent Blindness, Inc. JA is supported by NIH R01GM115650. The authors would like to thank Heather Blizard from the Albeck lab for assistance on electrotransfection. L.G. K.Z. and M.Z. developed the conception and designed the study, J.A. provided the MCF10A cell line and ERK reporter used in the research. L.G. and K.Z. collected most of the ERK modulation data and drafted the manuscript with help from all authors. L.G. M.P. and P. T. quantified the ERK dynamics. K.Z. did the transfection and ERK dynamic regulation experiment on PC12 cells. L.G. did the PC12 differentiation experiments, K.Z. and A.C. performed differentiation analysis. Q.Q. and W. L. contributed to the interpretation of the results. K.Z. finalized the manuscript with contributions from all authors. Min Zhao, John Albeck, Quan Qing and Liang Guo are named inventors with Houpu Li of a U.S. Patent application no. 16/675,127, filed November 5, 2019. Cell signaling pathway activation by local AC electric field. The patent is under consideration. The manuscript used some techniques described in the patent to regulate signaling dynamics. Arizona State University and University of California are patent applicants. We worked to ensure diversity in experimental samples through the selection of the cell lines. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
day = "19",
doi = "10.1016/j.isci.2021.103240",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "11",
}