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

Author:

Yaganoglu Sine,Kalyviotis KonstantinosORCID,Vagena-Pantoula ChristinaORCID,Jülich Dörthe,Gaub Benjamin M.,Welling Maaike,Lopes Tatiana,Lachowski DariuszORCID,Tang See Swee,Del Rio Hernandez ArmandoORCID,Salem VictoriaORCID,Müller Daniel J.ORCID,Holley Scott A.,Vermot Julien,Shi Jian,Helassa NordineORCID,Török KatalinORCID,Pantazis PeriklisORCID

Abstract

AbstractMechanosensing 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 vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease.

Funder

RCUK | Biotechnology and Biological Sciences Research Council

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

British Heart Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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