Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle

Abstract Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but...

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Autores principales:	Lorenzo Marcucci, Takumi Washio, Toshio Yanagida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b6ddf7f2e374f05ad8f3a2f6693920e
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spelling	oai:doaj.org-article:0b6ddf7f2e374f05ad8f3a2f6693920e2021-12-02T12:30:54ZTitin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle10.1038/s41598-017-05999-22045-2322https://doaj.org/article/0b6ddf7f2e374f05ad8f3a2f6693920e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05999-2https://doaj.org/toc/2045-2322Abstract Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat trabecula and whole ventricle. No additional regulatory mechanisms were considered in our model. Our simulations suggested that mechanosensing regulation is not limited to the initial phases of contraction but, instead, is crucial during physiological contraction. An important consequence of this finding is that titin mediated thick filament activation can account for several sarcomere length dependencies observed in contracting muscle. Under the hypothesis that a similar mechanism is acting on cardiac muscle, and within the limits of a finite element left ventricle model, we predict that these two regulatory mechanisms are crucial for the molecular basis of the Frank-Starling law of the heart.Lorenzo MarcucciTakumi WashioToshio YanagidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lorenzo Marcucci Takumi Washio Toshio Yanagida Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
description	Abstract Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat trabecula and whole ventricle. No additional regulatory mechanisms were considered in our model. Our simulations suggested that mechanosensing regulation is not limited to the initial phases of contraction but, instead, is crucial during physiological contraction. An important consequence of this finding is that titin mediated thick filament activation can account for several sarcomere length dependencies observed in contracting muscle. Under the hypothesis that a similar mechanism is acting on cardiac muscle, and within the limits of a finite element left ventricle model, we predict that these two regulatory mechanisms are crucial for the molecular basis of the Frank-Starling law of the heart.
format	article
author	Lorenzo Marcucci Takumi Washio Toshio Yanagida
author_facet	Lorenzo Marcucci Takumi Washio Toshio Yanagida
author_sort	Lorenzo Marcucci
title	Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
title_short	Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
title_full	Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
title_fullStr	Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
title_full_unstemmed	Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
title_sort	titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0b6ddf7f2e374f05ad8f3a2f6693920e
work_keys_str_mv	AT lorenzomarcucci titinmediatedthickfilamentactivationthroughamechanosensingmechanismintroducessarcomerelengthdependenciesinmathematicalmodelsofrattrabeculaandwholeventricle AT takumiwashio titinmediatedthickfilamentactivationthroughamechanosensingmechanismintroducessarcomerelengthdependenciesinmathematicalmodelsofrattrabeculaandwholeventricle AT toshioyanagida titinmediatedthickfilamentactivationthroughamechanosensingmechanismintroducessarcomerelengthdependenciesinmathematicalmodelsofrattrabeculaandwholeventricle
_version_	1718394257777098752

Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle

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