Chattaraj, S.; Zimmermann, J.; Pasqualini, F. S.

Morphogenesis involves biochemical and biomechanical interactions across multiple spatial and temporal scales. Experimental studies alone struggle to resolve these dynamics, necessitating computational models. Among these, subcellular element modeling (SEM) has proven helpful in simulating cellular and tissue-scale emergent behaviors. However, traditional SEM frameworks lack explicit representations of nuclear mechanics and cell-extracellular matrix (ECM) interactions, limiting their ability to capture key biology.\n\nHere, we introduce BIOPOINT, a particle-based computational framework that extends SEM by incorporating (1) a deformable, multi-particle nucleus to simulate nuclear stress and strain distributions and (2) an explicit ECM representation using a structured array of static particles interacting via tunable adhesive potentials. To ensure biological relevance, we calibrated BIOPOINTs parameters against single-cell indentation experiments, overcoming prior limitations of ad hoc parameter selection in SEM. We validate BIOPOINT by comparing simulated cell behaviors to experimental observations in three key scenarios: (i) single-cell indentation, demonstrating agreement with force-time curves from atomic force microscopy (AFM) studies; (ii) cell spreading on ECM micropatterns, confirming that nuclear deformation follows ECM constraints; and (iii) nuclear deformation during confined migration, showing BIOPOINT predicts nuclear shape dynamics as cells traverse constrictions accurately.\n\nBIOPOINT provides a computational framework for simulating nuclear mechanics and cell-ECM interactions with experimentally derived parameters. By integrating experimental data with a particle-based approach, BIOPOINT offers a practical tool for studying cell behavior that can inform future morphogenetic studies in-vivo or in-vitro.