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
Affiliations
Liang Guo
Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA; College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, Heilongjiang 150001, China
Kan Zhu
Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA
Michael Pargett
Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA
Adam Contreras
Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA
Patrick Tsai
Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA
Quan Qing
Department of Physics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
Wolfgang Losert
Department of Physics, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
John Albeck
Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA
Min Zhao
Department of Ophthalmology & Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA 95817, USA; Corresponding author
Summary: 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.
