Electrically synchronizing and modulating the dynamics of ERK activation to regulate cell fate

Liang Guo; Kan Zhu; Michael Pargett; Adam Contreras; Patrick Tsai; Quan Qing; Wolfgang Losert; John Albeck; Min Zhao

doi:10.1016/j.isci.2021.103240

Electrically synchronizing and modulating the dynamics of ERK activation to regulate cell fate

iScience. 2021 Oct 7;24(11):103240. doi: 10.1016/j.isci.2021.103240. eCollection 2021 Nov 19.

Authors

Liang Guo^{1

2}, Kan Zhu¹, Michael Pargett³, Adam Contreras¹, Patrick Tsai¹, Quan Qing⁴, Wolfgang Losert⁵, John Albeck³, Min Zhao¹

Affiliations

¹ Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA.
² College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, Heilongjiang 150001, China.
³ Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA.
⁴ Department of Physics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
⁵ Department of Physics, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.

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.

Grants and funding

R01 EY019101/EY/NEI NIH HHS/United States