ECMSim: A high-performance interactive web application for real-time spatiotemporal simulation of cardiac ECM...

Extracellular matrix (ECM) remodeling is central to a wide variety of healthy and diseased tissue processes. Unfortunately, predicting ECM remodeling under various chemical and mechanical conditions has proven to be excessively challenging, due in part to its complex regulation by intracellular and extracellular molecular reaction networks that are spatially and temporally dynamic. We introduce ECMSim, which is a highly interactive, real-time, and web application designed to simulate heterogeneous matrix remodeling. The current model simulates cardiac scar tissue with configurable input conditions using a large-scale model of the cardiac fibroblast signaling network. Cardiac fibrosis is a major component of many forms of heart failure. ECMSim solves 1.37 million coupled ordinary differential equations (ODEs) and executes approximately 4.84 million operations per time step in real time, encompassing 137 molecular species and 259 regulatory interactions per cell across a 100 × 100 spatial array (10,000 cells), which accounts for inputs, receptors, intracellular signaling cascades, ECM production, feedback loops, and molecular diffusion. The algorithm is represented by a set of ODEs that are coupled with ECM molecular diffusion. The equations are solved on demand using compiled C++ and the WebAssembly standard. The platform includes brush-style cell selection to target a subset of cells with adjustable input molecule concentrations, parameter sliders to adjust parameters on demand, and multiple coupled real-time visualizations of network dynamics at multiple scales. Implementing ECMSim in standard web technologies enables a fully functional application that combines real-time simulation, visual interaction, and model editing. The software enables the investigation of pathological or experimental conditions, hypothetical scenarios, matrix remodeling, or the testing of the effects of an experimental drug(s) with a target receptor.