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A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities

Garcia-Canadilla, P; Rodriguez, JF; Palazzi, MJ; Gonzalez-Tendero, A; Schönleitner, P; Balicevic, V; Loncaric, S; ... Bijnens, B; + view all (2017) A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities. PLoS ONE , 12 (8) , Article e0182915. 10.1371/journal.pone.0182915. Green open access

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Abstract

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca²⁺ release, Ca²⁺ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca²⁺ release and/or re-uptake, intra-cellular material properties, sarcomere proteins and distribution of the intracellular organelles. To investigate the possible causes of these heterogeneities, we developed a two-dimensional finite-element electromechanical model of a cardiomyocyte that takes into account the experimentally measured local deformation and cytosolic [Ca²⁺] to locally define the different variables of the constitutive equations describing the electro/mechanical behaviour of the cell. Then, the model was individualised to three different rat cardiac cells. The local [Ca²⁺] transients were used to define the [Ca²⁺]-dependent activation functions. The cell-specific local Young’s moduli were estimated by solving an inverse problem, minimizing the error between the measured and simulated local deformations along the longitudinal axis of the cell. We found that heterogeneities in the deformation during contraction were determined mainly by the local elasticity rather than the local amount of Ca²⁺, while in the relaxation phase deformation was mainly influenced by Ca²⁺ re-uptake. Our electromechanical model was able to successfully estimate the local elasticity along the longitudinal direction in three different cells. In conclusion, our proposed model seems to be a good approximation to assess the heterogeneous intracellular mechanical properties to help in the understanding of the underlying mechanisms of cardiomyocyte dysfunction.

Type: Article
Title: A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0182915
Publisher version: https://doi.org/10.1371/journal.pone.0182915
Language: English
Additional information: © 2017 Garcia-Canadilla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: Sarcomeres, Muscle contraction, Deformation, Cell biology, Mechanical properties, Cell physiology, Finite element analysis, Cellular structures and organelles
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10057618
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