A simple framework for agent-based modeling with extracellular matrix

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. 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 that addresses bidirectional cell-ECM interactions. We represent a small region of ECM, an ECM element, with 3 variables describing its local microstructure: anisotropy, density, and overall fiber orientation. We place an array of ECM elements to spatially model the ECM in a tissue. Cells remodel local ECM microstructure and in turn, local microstructure impacts cellular motility. We demonstrate the utility of this framework and the reusability of its core cell-ECM interaction model through examples in 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 that are of interest to the modeling community. Furthermore, in our framework, variables representing the ECM microstructure are available to impact all aspects of cell behavior such as proliferation and death. This presents a wide range of possibilities for future modelers to broadly explore cell-ECM interactions, extending currently available models and enabling rapid modeling of cell-matrix biology without requiring custom modeling code for each interaction. We make this framework available as a free and open source software package at . ### Competing Interest Statement The authors have declared no competing interest.