A Simple Framework for Agent-Based Modeling with Extracellular Matrix

Bulletin of Mathematical Biology, Journal Year: 2025, Volume and Issue: 87(3)

Published: Feb. 12, 2025

Abstract Extracellular matrix (ECM) is a key component of the cellular microenvironment and critical in multiple disease developmental processes. Representing ECM cell-ECM interactions challenging multiscale problem as they span molecular-level details to tissue-level dynamics. While several computational frameworks exist for modeling, often focus on very detailed modeling individual fibers or represent only single aspect ECM. Using PhysiCell agent-based platform, we developed framework intermediate detail with ability capture bidirectional interactions. We small region ECM, an element, three variables describing its local microstructure: anisotropy, density, overall fiber orientation. To spatially model use array elements. Cells remodel microstructure turn, impacts motility. demonstrate utility this reusability core interaction through examples invasion, wound healing, basement membrane degradation, leader-follower collective migration. Despite relative simplicity framework, it able broad range interest community. Furthermore, representing are accessible simple programming interfaces. This allows them impact cell behaviors, such proliferation death, without requiring custom code each interaction, particularly PhysiCell’s grammar, enabling rapid diverse cell-matrix biology. make available free open source software package at https://github.com/PhysiCell-Models/collective-invasion .

Language: Английский

A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 9, 2025

Metastasis, the leading cause of death in cancer patients, arises when cells disseminate from a primary solid tumour to distant organs. Growth and invasion often involve collective cell migration, which is profoundly influenced by cell-cell interactions extracellular matrix (ECM). The ECM's biochemical composition mechanical properties, such as stiffness, regulate behaviour migration dynamics. Mathematical modelling serves pivotal tool for studying predicting these complex dynamics, with hybrid discrete-continuous models offering powerful approach combining agent-based representations continuum descriptions surrounding microenvironment. In this study, we investigate impact ECM modulated via ribose-induced collagen cross-linking, on spheroid growth invasion. We employed model implemented PhysiCell simulate successfully replicating three-dimensional vitro experiments. incorporates detailed cell-ECM interactions, remodelling, proliferation. Our simulations align experimental observations two breast lines, non-invasive MCF7 invasive HCC 1954, under varying stiffness conditions. results demonstrate that increased due cross-linking inhibits cells, whereas remain largely unaffected. Furthermore, our show higher degradation not only enables but also facilitates formation multicellular protrusions. Conversely, increasing maximum speed can reach enhances while promoting single-cell This understanding interplay between proliferation, paving way future studies incorporating additional characteristics microenvironmental

Language: Английский

A simple framework for agent-based modeling with extracellular matrix

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 22, 2022

Abstract Extracellular matrix (ECM) is a key component of the cellular microenvironment and critical in multiple disease developmental processes. Representing ECM cell-ECM interactions challenging multiscale problem as they span molecular-level details to tissue-level dynamics. While several computational frameworks exist for modeling, often focus on very detailed modeling individual fibers or represent only single aspect ECM. Using PhysiCell agent-based platform, we developed framework intermediate detail with ability capture bidirectional interactions. We small region ECM, an element, three variables describing its local microstructure: anisotropy, density, overall fiber orientation. To spatially model use array elements. Cells remodel microstructure turn, impacts motility. demonstrate utility this reusability core interaction through examples invasion, wound healing, basement membrane degradation, leader-follower collective migration. Despite relative simplicity framework, it able broad range interest community. Furthermore, representing are accessible simple programming interfaces. This allows them impact cell behaviors, such proliferation death, without requiring custom code each interaction, particularly PhysiCell’s grammar, enabling rapid diverse cell-matrix biology. make available free open source software package at https://github.com/PhysiCell-Models/collective-invasion .

Language: Английский