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

Abstract

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

Metadata

Item Type:	Article
Authors/Creators:	Yaganoglu, S. Kalyviotis, K. https://orcid.org/0000-0002-7640-8905 Vagena-Pantoula, C. https://orcid.org/0000-0002-3591-2267 Jülich, D. Gaub, B.M. Welling, M. Lopes, T. Lachowski, D. https://orcid.org/0000-0003-1194-8019 Tang, S.S. Del Rio Hernandez, A. https://orcid.org/0000-0001-5062-8910 Salem, V. https://orcid.org/0000-0001-6463-7471 Müller, D.J. https://orcid.org/0000-0003-3075-0665 Holley, S.A. Vermot, J. Shi, J. Helassa, N. https://orcid.org/0000-0003-3743-1886 Török, K. https://orcid.org/0000-0002-3107-4534 Pantazis, P. https://orcid.org/0000-0002-8367-9332
Copyright, Publisher and Additional Information:	© The Author(s) 2023, corrected publication 2023 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Cell Membrane; Ion Channels; Mechanotransduction, Cellular; Mechanical Phenomena
Dates:	Published: 19 July 2023 Published (online): 19 July 2023 Accepted: 11 July 2023
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds)
Funding Information:	Funder Grant number British Heart Foundation FS/17/2/32559 British Heart Foundation PG/21/10595
Depositing User:	Symplectic Publications
Date Deposited:	09 Apr 2024 11:43
Last Modified:	09 Apr 2024 11:43
Published Version:	http://dx.doi.org/10.1038/s41467-023-40134-y
Status:	Published
Publisher:	Springer Science and Business Media LLC
Identification Number:	10.1038/s41467-023-40134-y
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:206602

Commentary/Response Threads

Yaganoglu, S., Kalyviotis, K., Vagena-Pantoula, C., Jülich, D., Gaub, B.M., Welling, M., Lopes, T., Lachowski, D., Tang, S.S., Del Rio Hernandez, A., Salem, V., Müller, D.J., Holley, S.A., Vermot, J., Shi, J., Helassa, N., Török, K. and Pantazis, P. Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi. (deposited 09 Apr 2024 11:43) [Currently Displayed]
- Yaganoglu, S., Kalyviotis, K., Vagena-Pantoula, C., Jülich, D., Gaub, B.M., Welling, M., Lopes, T., Lachowski, D., Tang, S.S., Del Rio Hernandez, A., Salem, V., Müller, D.J., Holley, S.A., Vermot, J., Shi, J., Helassa, N., Török, K. and Pantazis, P. Author Correction: Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi. (deposited 15 Dec 2023 17:22)

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