Cellfoundry: a GPU-accelerated, multi-physics ABM framework for cellular microenvironment and organoid-scale studies

Abstract

Advanced in vitro systems such as organoids and microfluidic organ-on-a-chip platforms enable physiologically richer experimentation, but their complexity creates large parameter spaces and makes it difficult to disentangle the mechanistic roles of transport, mechanics, and extracellular microstructure. Agent-based modelling provides a natural computational counterpart to these systems by representing heterogeneous cells as discrete entities coupled through local rules and environmental fields. However, realistic microenvironment models often remain limited by scalability, simplified extracellular matrix representations, and the practical difficulty of calibrating large numbers of parameters. Here we present Cellfoundry, a computational framework built on a FLAMEGPU2-based modelling template for simulating complex cellular microenvironments. The framework integrates multiple interacting agent populations, including cells, fibrous networks, and focal adhesions mediating attachment dynamics and traction-force transmission. It combines mechanically resolved cell-cell and cell-matrix interactions with multi-species diffusion fields that propagate biochemical signals through the extracellular environment and regulate processes such as metabolism, migration, and cell-cycle progression. Cellfoundry also supports customizable behaviours across multiple cell types, enabling the study of heterogeneous multicellular systems within a unified computational setting. To support reproducible model development and calibration, the framework includes a fibre-network generation module, automated performance benchmarking workflows, post-processing and reporting utilities, and an Optuna-based Bayesian optimization pipeline with configurable single- and multi-objective targets. Two showcase examples illustrate these capabilities: a migration assay calibrated against fibroblast motility descriptors and a multi-objective organoid growth scenario reproducing target population composition and expansion dynamics and over time. Together, these examples demonstrate how Cellfoundry can be used to build, calibrate, and extend mechanistically interpretable models of coupled biochemical and mechanical dynamics in advanced in vitro systems. HighlightsO_LIHighly versatile, GPU-accelerated agent-based framework for cellular microenvironments C_LIO_LIExplicit fibrous ECM networks with dynamic remodelling and focal adhesion agents C_LIO_LICoupled mechanics and multi-species diffusion regulate cell behaviour in a highly customizable environment C_LIO_LIModular architecture with automated benchmarking and Bayesian parameter optimization C_LI