Virtual cardiac monolayers for electrical wave propagation

Kudryashova, Nina; Tsvelaya, V. A.; Agladze, Konstantin; Panfilov, Alexander V.

doi:10.1038/s41598-017-07653-3

Cited by 19 publications

(38 citation statements)

References 66 publications

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“…The cardiomyocytes were not located randomly but organised in a 52 branching network that wired the whole sample. 53 Next, in order to explain cardiac network formation, we applied a virtual cardiac 54 monolayer framework developed in [15], based on the Cellular Potts Models [16][17][18]. We 55 proposed a hypothesis that such self-organisation occurs due to cytoskeletons' alignment.…”

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confidence: 99%

“…Second, we analyse the patterns and formulate the 63 hypothesis on the mechanism of their formation. Third, we implement the hypothesis 64 and reproduce pattern formation in silico in a Cellular Potts Model (CPM) of cardiac 65 tissue [15]. Next, we compare electrical signal propagation in computer modelling and in 66 experiments.…”

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confidence: 99%

“…The tension is maximal, if the actin filaments are aligned with each 125 other, which gives a preference for intercellular alignment of the cytoskeletons. 126 Therefore, we have incorporated this mechanism into our Cellular Potts Model 127 (CPM) of cardiac cells [15]. This model was already adjusted to reproduce characteristic 128 shapes of the cardiac cells in virtual tissue model, and here we extended it with a new 129 energy term, that corresponded to the alignment of actin bundles in the neighbouring 130 cells.…”

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confidence: 99%

“…For manual 339 counting cells' nuclei stained with DAPI represented the overall number of cells, while 340 only those within α-actinin stained fibers were accounted for cardiomyocytes. The 341 second method was performed on cytofluorometer (Accuri C6, BD Biosciences, USA) by 342 distinguishing non-cardiomyocytes, stained only for F-actin, from CMs, stained both for 343 F-actin and α-actinin 344 Mathematical model for cardiac tissue growth 345 In this study, we have used a mathematical model that was previously developed for 346 cardiac monolayers formation [15]. It is based on the Cellular Potts Model (CPM) 347 formalism, which describes cells as the domains of the regular lattice and assigns energy 348 to the system of cells to describe their growth and motility.…”

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confidence: 99%

“…It is based on the Cellular Potts Model (CPM) 347 formalism, which describes cells as the domains of the regular lattice and assigns energy 348 to the system of cells to describe their growth and motility. In our previous work [15], we 349 have selected the main features of the cardiac cells (such as area, number of protrusions, 350 etc.) and parametrised our model to reproduce the cell shapes.…”

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confidence: 99%

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Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fibrosis

Kudryashova

Nizamieva²,

Tsvelaya³

et al. 2018

Preprint

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Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors. Regions with a high density of fibrosis are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias. Therefore, studies of the wave propagation through these regions are very important, yet the precise mechanisms leading to arrhythmia formation in fibrotic cardiac tissue remain poorly understood. Particularly, it is not clear how wave propagation is organized at the cellular level, as experiments show that the regions with a high percentage of fibrosis (65-75%) are still conducting electrical signals, whereas geometric analysis of randomly distributed cells predicts connectivity loss at 40% at the most (percolation threshold). To address this question, we used a joint in vitro-in silico approach, which combined experiments in neonatal rat cardiac monolayers with morphological and electrophysiological computer simulations. We have shown that the main reason for sustainable wave propagation in highly fibrotic samples is the formation of a branching network of cardiomyocytes. We have successfully reproduced the morphology of conductive pathways in computer modelling, assuming that cardiomyocytes align their cytoskeletons to fuse into cardiac syncytium. The electrophysiological properties of the monolayers, such as conduction velocity, conduction blocks and wave fractionation, were reproduced as well. In a virtual cardiac tissue, we have also examined the wave propagation at the subcellular level, detected wavebreaks formation and its relation to the structure of fibrosis and, thus, analysed the processes leading to the onset of arrhythmias.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fibrosis

Kudryashova

Nizamieva²,

Tsvelaya³

et al. 2018

Preprint

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Adapting a Plant Tissue Model to Animal Development: Introducing Cell Sliding into VirtualLeaf

2019

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Cell-based, mathematical modeling of collective cell behavior has become a prominent tool in developmental biology. Cell-based models represent individual cells as single particles or as sets of interconnected particles and predict the collective cell behavior that follows from a set of interaction rules. In particular, vertex-based models are a popular tool for studying the mechanics of confluent, epithelial cell layers. They represent the junctions between three (or sometimes more) cells in confluent tissues as point particles, connected using structural elements that represent the cell boundaries. A disadvantage of these models is that cell–cell interfaces are represented as straight lines. This is a suitable simplification for epithelial tissues, where the interfaces are typically under tension, but this simplification may not be appropriate for mesenchymal tissues or tissues that are under compression, such that the cell–cell boundaries can buckle. In this paper, we introduce a variant of VMs in which this and two other limitations of VMs have been resolved. The new model can also be seen as on off-the-lattice generalization of the Cellular Potts Model. It is an extension of the open-source package VirtualLeaf, which was initially developed to simulate plant tissue morphogenesis where cells do not move relative to one another. The present extension of VirtualLeaf introduces a new rule for cell–cell shear or sliding, from which cell rearrangement (T1) and cell extrusion (T2) transitions emerge naturally, allowing the application of VirtualLeaf to problems of animal development. We show that the updated VirtualLeaf yields different results than the traditional vertex-based models for differential adhesion-driven cell sorting and for the neighborhood topology of soft cellular networks. Electronic supplementary material The online version of this article (10.1007/s11538-019-00599-9) contains supplementary material, which is available to authorized users.

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Assessing the origin and velocity of Ca2+ waves in three-dimensional tissue: Insights from a mathematical model and confocal imaging in mouse pancreas tissue slices

Šterk

Dolenšek

Bombek

et al. 2021

Communications in Nonlinear Science and Numerical Simulation

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Virtual cardiac monolayers for electrical wave propagation

Cited by 19 publications

References 66 publications

Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fibrosis

Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fibrosis

Adapting a Plant Tissue Model to Animal Development: Introducing Cell Sliding into VirtualLeaf

Assessing the origin and velocity of Ca2+ waves in three-dimensional tissue: Insights from a mathematical model and confocal imaging in mouse pancreas tissue slices

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