Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi

Session

Session 6 - Imaging Across Scales

Authors

Periklis (Laki) Pantazis (1)

Affiliations

1. Imperial College London

Keywords

Piezo1, mechanobiology, imaging across scales

Abstract text

Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescent reporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate that GenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-cell level to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in the plasma membrane of single cells, resolves repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in life zebrafish. In addition, we show how GenEPi and other similar biosensors can be used to monitor Piezo1 activity in several mechanochemical feedback loops during development, homeostatic regulation, and disease.

References

Pantazis, P. & Supatto, W. Advances in whole-embryo imaging: a quantitative transition is underway. Nat Rev Mol Cell Biol 15, 327-339, doi:10.1038/nrm3786 (2014).

Yaganoglu, S., Kalyviotis, K. et al. Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi. Nat Commun. 14(1):4352. doi: 10.1038/s41467-023-40134-y (2023).