OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue

Abstract Intercellular electrical coupling is an essential means of communication between cells. It is important to obtain quantitative knowledge of such coupling between cardiomyocytes and non-excitable cells when, for example, pathological electrical coupling between myofibroblasts and cardiomyocy...

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Autores principales:	Patrick M. Boyle, Jinzhu Yu, Aleksandra Klimas, John C. Williams, Natalia A. Trayanova, Emilia Entcheva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/161667824bf64f7aa858a0b80b9a1630
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spelling	oai:doaj.org-article:161667824bf64f7aa858a0b80b9a16302021-12-02T16:56:02ZOptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue10.1038/s41598-021-88573-12045-2322https://doaj.org/article/161667824bf64f7aa858a0b80b9a16302021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88573-1https://doaj.org/toc/2045-2322Abstract Intercellular electrical coupling is an essential means of communication between cells. It is important to obtain quantitative knowledge of such coupling between cardiomyocytes and non-excitable cells when, for example, pathological electrical coupling between myofibroblasts and cardiomyocytes yields increased arrhythmia risk or during the integration of donor (e.g., cardiac progenitor) cells with native cardiomyocytes in cell-therapy approaches. Currently, there is no direct method for assessing heterocellular coupling within multicellular tissue. Here we demonstrate experimentally and computationally a new contactless assay for electrical coupling, OptoGap, based on selective illumination of inexcitable cells that express optogenetic actuators and optical sensing of the response of coupled excitable cells (e.g., cardiomyocytes) that are light-insensitive. Cell–cell coupling is quantified by the energy required to elicit an action potential via junctional current from the light-stimulated cell(s). The proposed technique is experimentally validated against the standard indirect approach, GapFRAP, using light-sensitive cardiac fibroblasts and non-transformed cardiomyocytes in a two-dimensional setting. Its potential applicability to the complex three-dimensional setting of the native heart is corroborated by computational modelling and proper calibration. Lastly, the sensitivity of OptoGap to intrinsic cell-scale excitability is robustly characterized via computational analysis.Patrick M. BoyleJinzhu YuAleksandra KlimasJohn C. WilliamsNatalia A. TrayanovaEmilia EntchevaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrick M. Boyle Jinzhu Yu Aleksandra Klimas John C. Williams Natalia A. Trayanova Emilia Entcheva OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
description	Abstract Intercellular electrical coupling is an essential means of communication between cells. It is important to obtain quantitative knowledge of such coupling between cardiomyocytes and non-excitable cells when, for example, pathological electrical coupling between myofibroblasts and cardiomyocytes yields increased arrhythmia risk or during the integration of donor (e.g., cardiac progenitor) cells with native cardiomyocytes in cell-therapy approaches. Currently, there is no direct method for assessing heterocellular coupling within multicellular tissue. Here we demonstrate experimentally and computationally a new contactless assay for electrical coupling, OptoGap, based on selective illumination of inexcitable cells that express optogenetic actuators and optical sensing of the response of coupled excitable cells (e.g., cardiomyocytes) that are light-insensitive. Cell–cell coupling is quantified by the energy required to elicit an action potential via junctional current from the light-stimulated cell(s). The proposed technique is experimentally validated against the standard indirect approach, GapFRAP, using light-sensitive cardiac fibroblasts and non-transformed cardiomyocytes in a two-dimensional setting. Its potential applicability to the complex three-dimensional setting of the native heart is corroborated by computational modelling and proper calibration. Lastly, the sensitivity of OptoGap to intrinsic cell-scale excitability is robustly characterized via computational analysis.
format	article
author	Patrick M. Boyle Jinzhu Yu Aleksandra Klimas John C. Williams Natalia A. Trayanova Emilia Entcheva
author_facet	Patrick M. Boyle Jinzhu Yu Aleksandra Klimas John C. Williams Natalia A. Trayanova Emilia Entcheva
author_sort	Patrick M. Boyle
title	OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
title_short	OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
title_full	OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
title_fullStr	OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
title_full_unstemmed	OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
title_sort	optogap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/161667824bf64f7aa858a0b80b9a1630
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OptoGap is an optogenetics-enabled assay for quantification of cell–cell coupling in multicellular cardiac tissue

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