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research article

Active contraction of cardiac cells: a reduced model for sarcomere dynamics with cooperative interactions

Regazzoni, Francesco
•
Dede, Luca  
•
Quarteroni, Alfio  
December 1, 2018
Biomechanics And Modeling In Mechanobiology

We propose a reduced ODE model for the mechanical activation of cardiac myofilaments, which is based on explicit spatial representation of nearest-neighbour interactions. Our model is derived from the cooperative Markov Chain model of Washio et al. (Cell Mol Bioeng 5(1):113-126, 2012), under the assumption of conditional independence of specific sets of events. This physically motivated assumption allows to drastically reduce the number of degrees of freedom, thus resulting in a significantly large computational saving. Indeed, the original Markov Chain model involves a huge number of degrees of freedom (order of 1021) and is solved by means of the Monte Carlo method, which notoriously reaches statistical convergence in a slow fashion. With our reduced model, instead, numerical simulations can be carried out by solving a system of ODEs, reducing the computational time by more than 10,000 times. Moreover, the reduced model is accurate with respect to the original Markov Chain model. We show that the reduced model is capable of reproducing physiological steady-state force-calcium and force-length relationships with the observed asymmetry in apparent cooperativity near the calcium level producing half activation. Finally, we also report good qualitative and quantitative agreement with experimental measurements under dynamic conditions.

  • Details
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Type
research article
DOI
10.1007/s10237-018-1049-0
Web of Science ID

WOS:000452359300007

Author(s)
Regazzoni, Francesco
Dede, Luca  
Quarteroni, Alfio  
Date Issued

2018-12-01

Publisher

SPRINGER HEIDELBERG

Published in
Biomechanics And Modeling In Mechanobiology
Volume

17

Issue

6

Start page

1663

End page

1686

Subjects

Biophysics

•

Engineering, Biomedical

•

Engineering

•

cardiac tension development

•

mathematical modelling

•

crossbridge

•

sarcomere dynamics

•

cooperativity

•

tension development

•

mechanical-properties

•

intracellular ca2+

•

strong-binding

•

thin filament

•

muscle

•

activation

•

length

•

intact

•

simulation

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
CMCS  
Available on Infoscience
December 20, 2018
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/153121
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