Traction force microscopy of engineered cardiac tissues.

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the cl...

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Main Authors: Francesco Silvio Pasqualini, Ashutosh Agarwal, Blakely Bussie O'Connor, Qihan Liu, Sean P Sheehy, Kevin Kit Parker
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5874032?pdf=render
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author Francesco Silvio Pasqualini
Ashutosh Agarwal
Blakely Bussie O'Connor
Qihan Liu
Sean P Sheehy
Kevin Kit Parker
author_facet Francesco Silvio Pasqualini
Ashutosh Agarwal
Blakely Bussie O'Connor
Qihan Liu
Sean P Sheehy
Kevin Kit Parker
author_sort Francesco Silvio Pasqualini
collection DOAJ
description Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.
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spelling doaj.art-db0275afac4b4fb2992a2891e1f175bb2022-12-21T18:39:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019470610.1371/journal.pone.0194706Traction force microscopy of engineered cardiac tissues.Francesco Silvio PasqualiniAshutosh AgarwalBlakely Bussie O'ConnorQihan LiuSean P SheehyKevin Kit ParkerCardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.http://europepmc.org/articles/PMC5874032?pdf=render
spellingShingle Francesco Silvio Pasqualini
Ashutosh Agarwal
Blakely Bussie O'Connor
Qihan Liu
Sean P Sheehy
Kevin Kit Parker
Traction force microscopy of engineered cardiac tissues.
PLoS ONE
title Traction force microscopy of engineered cardiac tissues.
title_full Traction force microscopy of engineered cardiac tissues.
title_fullStr Traction force microscopy of engineered cardiac tissues.
title_full_unstemmed Traction force microscopy of engineered cardiac tissues.
title_short Traction force microscopy of engineered cardiac tissues.
title_sort traction force microscopy of engineered cardiac tissues
url http://europepmc.org/articles/PMC5874032?pdf=render
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AT ashutoshagarwal tractionforcemicroscopyofengineeredcardiactissues
AT blakelybussieoconnor tractionforcemicroscopyofengineeredcardiactissues
AT qihanliu tractionforcemicroscopyofengineeredcardiactissues
AT seanpsheehy tractionforcemicroscopyofengineeredcardiactissues
AT kevinkitparker tractionforcemicroscopyofengineeredcardiactissues