摘要：SummaryIntracellular 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 behaviorsin vivowithout the use of biochemical agents or genetic manipulation.Graphical abstractDisplay OmittedHighlights•Alternating-current (AC) electric field activates ERK independently of growth factors•AC stimulation length modulates the amplitude and duration of ERK activation•On-off time interval of AC modulates the frequency of ERK activation peaks•Electrical modulation of ERK dynamics promotes neuronal differentiation of PC12 cellsBiotechnology; Cell biology; Integrative aspects of cell biology; Functional aspects of cell biology
