Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Marcel Schubert; Lewis Woolfson; Isla R. M. Barnard; Amy M. Dorward; Becky Casement; Andrew Morton; Gavin B. Robertson; Paul L. Appleton; Gareth B. Miles; Carl S. Tucker; Samantha J. Pitt; Malte C. Gather

doi:10.1038/s41566-020-0631-z

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Marcel Schubert (Lead / Corresponding author), Lewis Woolfson, Isla R. M. Barnard, Amy M. Dorward, Becky Casement, Andrew Morton, Gavin B. Robertson, Paul L. Appleton, Gareth B. Miles, Carl S. Tucker, Samantha J. Pitt, Malte C. Gather

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Abstract

The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

Original language	English
Pages (from-to)	452-458
Number of pages	7
Journal	Nature Photonics
Volume	14
Issue number	7
Early online date	15 Jun 2020
DOIs	https://doi.org/10.1038/s41566-020-0631-z
Publication status	Published - Jul 2020

Keywords

Biophotonics
Biophysics
Imaging and sensing
Microscopy
Optical spectroscopy

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Atomic and Molecular Physics, and Optics

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10.1038/s41566-020-0631-z

Author Accepted ManuscriptAccepted author manuscript, 5.14 MB

Cite this

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title = "Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers",

abstract = "The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.",

keywords = "Biophotonics, Biophysics, Imaging and sensing, Microscopy, Optical spectroscopy",

author = "Marcel Schubert and Lewis Woolfson and Barnard, {Isla R. M.} and Dorward, {Amy M.} and Becky Casement and Andrew Morton and Robertson, {Gavin B.} and Appleton, {Paul L.} and Miles, {Gareth B.} and Tucker, {Carl S.} and Pitt, {Samantha J.} and Gather, {Malte C.}",

note = "This research was financially supported by the European Research Council under the European Union{\textquoteright}s Horizon 2020 Framework Programme (FP/2014-2020)/ERC grant agreement no. 640012 (ABLASE), by EPSRC (grant no. EP/P030017/1) and by the RS Macdonald Charitable Trust. S.J.P. acknowledges funding by the Royal Society of Edinburgh (Biomedical Fellowship) and the British Heart Foundation (grant no. FS/17/9/32676). S.J.P. and G.B.R. acknowledge support from The Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews (grant no. 204821/Z/16/A). M.S. acknowledges funding by the European Commission (Marie Sk{\l}odowska-Curie Individual Fellowship, 659213) and the Royal Society (Dorothy Hodgkin Fellowship, DH160102; grant no. RGF\R1\180070).",

year = "2020",

month = jul,

doi = "10.1038/s41566-020-0631-z",

language = "English",

volume = "14",

pages = "452--458",

journal = "Nature Photonics",

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T1 - Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

AU - Schubert, Marcel

AU - Woolfson, Lewis

AU - Barnard, Isla R. M.

AU - Dorward, Amy M.

AU - Casement, Becky

AU - Morton, Andrew

AU - Robertson, Gavin B.

AU - Appleton, Paul L.

AU - Miles, Gareth B.

AU - Tucker, Carl S.

AU - Pitt, Samantha J.

AU - Gather, Malte C.

N1 - This research was financially supported by the European Research Council under the European Union’s Horizon 2020 Framework Programme (FP/2014-2020)/ERC grant agreement no. 640012 (ABLASE), by EPSRC (grant no. EP/P030017/1) and by the RS Macdonald Charitable Trust. S.J.P. acknowledges funding by the Royal Society of Edinburgh (Biomedical Fellowship) and the British Heart Foundation (grant no. FS/17/9/32676). S.J.P. and G.B.R. acknowledge support from The Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews (grant no. 204821/Z/16/A). M.S. acknowledges funding by the European Commission (Marie Skłodowska-Curie Individual Fellowship, 659213) and the Royal Society (Dorothy Hodgkin Fellowship, DH160102; grant no. RGF\R1\180070).

PY - 2020/7

Y1 - 2020/7

N2 - The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

AB - The contractility of cardiac cells is a key parameter that describes the biomechanical characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resolution remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein density as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiological parameters with cellular resolution.

KW - Biophotonics

KW - Biophysics

KW - Imaging and sensing

KW - Microscopy

KW - Optical spectroscopy

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DO - 10.1038/s41566-020-0631-z

M3 - Article

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SN - 1749-4885

VL - 14

SP - 452

EP - 458

JO - Nature Photonics

JF - Nature Photonics

IS - 7

ER -

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

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A Fully Integrated FLIM-FRET System For Imaging Dynamic Protein - Protein Interactions And Protein Turnover In Single Live Cells And Model Organisms

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Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Abstract

Keywords

ASJC Scopus subject areas

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A Fully Integrated FLIM-FRET System For Imaging Dynamic Protein - Protein Interactions And Protein Turnover In Single Live Cells And Model Organisms

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