Fig 1.
Multiscale cardiac cell workflow.
The main interface workflow contains single-cell or zero-dimension (SingleCell-Sim—black circle symbol), one-dimension (OneD-Sim—black rectangle symbol), and two-dimension (TwoD-Sim—black square symbol) tissue simulation modules, as well as user configuration parameters.
Fig 2.
The module “SingleCellUsrConf” is the User Configuration Module for single-cell simulations (SingleCell-Sim, see Fig 1). We created the user configuration module to allow users to control simulation constraints such as Na+ and rapid delayed rectifier K+ channel (IKr) blocker concentrations, ligand (β-blocker isoproterenol) concentration, CaMKII activity levels, number of beats, basic cycle length (BCL) i.e. heartbeat duration and other controls for single-cell simulation through workflow parameters.
Fig 3.
The “SingleCellMod” module is the Core Simulation Module for single-cell simulations (SingleCell-Sim, see Fig 1). The Kepler’s Execution Choice actor was created to provide user options of multiple computing platforms based on the use case, data size and the resource availability.
Fig 4.
Simulated human ventricular single-cell model via kepler workflow with or without IKr reduction.
A. User configurations are shown in the left panels. Simulated single-cell action potential (AP–middle panel), and the time course of original IKr (control) during the AP (bottom). B—D Simulated single-cell action potentials (middle) with reduced IKr (bottom). GKr block ratio was set to 0.75 (B), 0.5 (C) and 0.25 (D) in 0D configuration setting (green arrows–left panels), corresponding to 25, 50 or 75% IKr block, respectively.
Fig 5.
The workflow integrates multistep 0D (single-cell), 1D and 2D model simulations in a single automated process.
A. Simulated results of single-cell action potential (bottom panel). B. The pseudo ECG (bottom panel), and C. Six distinct time snapshots of 2D action potential wave propagation (bottom panel) from endocardial region (left) to epicardial region (right), with a linear decrease in APDs.
Fig 6.
Simulated multispecies ventricular single-cell (0D) and 1D simulations depending on user choice.
The multiscale cardiac cell modeling workflow presents from 0-Dimension (circle) to 1-Dimension (rectangle). A—C. Pseudo-ECGs were computed in the Human (orange), Rabbit (purple) and Mouse (green) ventricular cell models.