Bimodal patterns of Piezo1-mediated intracellular signaling

What is it about?

Piezo1 belongs to mechano-activatable cation channels serving as biological force sensors and regulates vascular development, blood pressure and exercise performance, epithelial cell crowding and division. The discovery of Piezo1 is the main reason for the Nobel Prize in Physiology, 2021. However, it remains unclear how cells perceive mechanical cues of the external microenvironment and transduce them into molecular signals and genetic regulations for the coordination of cellular responses. We have investigated Piezo1 activation and its effects on downstream signaling with a live cell imaging system based on fluorescence resonance energy transfer (FRET) and, for the first time, revealed a bimodal pattern of Piezo1-induced intracellular calcium signaling, utilizing a unique mechanical laser-induced shockwave (LIS) or chemical Yoda1 ligand stimulation. The results showed that a strong Piezo1 activation leads to a sustained calcium signal and a suppression of FAK activity. In contrast, a moderate Piezo1 activation results in a transient calcium signal and an increase of FAK activity. These findings revealed a precisely tuned Piezo1 response to external stimuli with different strengths.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

The combination of the two photonic approaches, laser-induced shockwaves (LIS) and FRET microscopy, establishes a broadly applicable and unique approach to introduce local mechanical perturbations precisely and visualize the spatiotemporal dynamics and transmission of subsequent signaling events directly. The bimodal pattern of Piezo1-induced intracellular signaling revealed in this study should shed new light on how the mechanosensitive Piezo1 regulates cell adhesion and paves the way to a better understanding of Piezo1-related mechanotransduction in both physiological and disease processes.