A comprehensive multiscale framework for simulating optogenetics in the heart

Patrick M. Boyle; John C. Williams; Christina M. Ambrosi; Emilia Entcheva; Natalia A. Trayanova

doi:10.1038/ncomms3370

A comprehensive multiscale framework for simulating optogenetics in the heart

Patrick M. Boyle, John C. Williams, Christina M. Ambrosi, Emilia Entcheva, Natalia A. Trayanova

Whiting School of Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.

Original language	English (US)
Article number	2370
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3370
State	Published - 2013

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms3370

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title = "A comprehensive multiscale framework for simulating optogenetics in the heart",

abstract = "Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.",

author = "Boyle, {Patrick M.} and Williams, {John C.} and Ambrosi, {Christina M.} and Emilia Entcheva and Trayanova, {Natalia A.}",

note = "Funding Information: P.M.B. is supported by a fellowship from the Natural Sciences and Engineering Research Council of Canada. This research was also supported by the US National Institutes of Health, grants R01 HL111649 and R01 HL103428, and by the US National Science Foundation, grants NSF-CDI-1124804 and NSF-OCI-108849.",

year = "2013",

doi = "10.1038/ncomms3370",

language = "English (US)",

volume = "4",

journal = "Nature Communications",

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T1 - A comprehensive multiscale framework for simulating optogenetics in the heart

AU - Boyle, Patrick M.

AU - Williams, John C.

AU - Ambrosi, Christina M.

AU - Entcheva, Emilia

AU - Trayanova, Natalia A.

N1 - Funding Information: P.M.B. is supported by a fellowship from the Natural Sciences and Engineering Research Council of Canada. This research was also supported by the US National Institutes of Health, grants R01 HL111649 and R01 HL103428, and by the US National Science Foundation, grants NSF-CDI-1124804 and NSF-OCI-108849.

PY - 2013

Y1 - 2013

N2 - Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.

AB - Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.

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A comprehensive multiscale framework for simulating optogenetics in the heart

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