A Simple Framework for Agent-Based Modeling with Extracellular Matrix

作者：John Metzcar, Ben Duggan, Brandon Fischer, Matthew C. Murphy, Randy Heiland, Paul Macklin · 发表于：Bulletin of Mathematical Biology · 年份：2025 · DOI：10.1007/s11538-024-01408-8 · 被引用次数：10 · 研究领域：Cellular Mechanics and Interactions、Mathematical Biology Tumor Growth、3D Printing in Biomedical Research

Extracellular matrix (ECM) is a key component of the cellular microenvironment and critical in multiple disease and developmental processes. Representing ECM and cell-ECM interactions is a challenging multiscale problem as they span molecular-level details to tissue-level dynamics. While several computational frameworks exist for ECM modeling, they often focus on very detailed modeling of individual ECM fibers or represent only a single aspect of the ECM. Using the PhysiCell agent-based modeling platform, we developed a framework of intermediate detail with the ability to capture bidirectional cell-ECM interactions. We represent a small region of ECM, an ECM element, with three variables describing its local microstructure: anisotropy, density, and overall fiber orientation. To spatially model the ECM, we use an array of ECM elements. Cells remodel local ECM microstructure and in turn, local microstructure impacts cellular motility. We demonstrate the utility of this framework and reusability of its core cell-ECM interaction model through examples in cellular invasion, wound healing, basement membrane degradation, and leader-follower collective migration. Despite the relative simplicity of the framework, it is able to capture a broad range of cell-ECM interactions of interest to the modeling community. Furthermore, variables representing the ECM microstructure are accessible through simple programming interfaces. This allows them to impact cell behaviors, such as proliferatio...