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

Session

Imaging Biomechanics

Authors

Dr Sine Yaganoglu* (1), Dr Konstantinos Kalyviotis* (2), Christina Vagena-Pantoula (2), Dr Dörthe Jülich (6), Dr Benjamin Gaub (1), Dr Maaike Welling (1, 2), Tatiana Lopes (2), Dr Dariusz Lachowski (2), See Swee Tang (2), Dr Armando Del Rio Hernandez (2), Dr Victoria Salem (2), Prof Daniel Müller (1), Prof Scott Holley (6), Dr Julien Vermot (2), Dr Jian Shi (4), Dr Nordine Helassa (5), Prof Katalin Török (3), Dr Periklis Pantazis (2, 1)

Affiliations

1. ETH Zurich
2. Imperial College London
3. St. George’s, University of London
4. Univeristy of Leeds
5. University of Liverpool
6. Yale University

Keywords

Piezo1, mechanosensing, optical imaging, genetically-encoded reporter

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 have been mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we developed 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 revealed transient, local mechanical stimuli in the plasma membrane of single cells, resolved repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allowed for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease.

References

https://www.biorxiv.org/content/10.1101/702423v1