PLoS Comput Biol. 2026 Mar 31. 22(3):
e1014113
Morphogenesis arises from biochemical and biomechanical interactions across multiple spatial and temporal scales. Experimental studies alone cannot fully resolve these dynamics, motivating computational models. Subcellular element modeling (SEM) is well suited for simulating emergent cellular and tissue morphologies, but traditional SEM frameworks do not explicitly include nuclear deformation or direct cell-extracellular matrix (ECM) interactions: capabilities typically associated with continuum approaches based on the finite-element method (FEM) approaches, FEM excels at modeling cell and tissue mechanics, but struggle to accommodate the large, non-linear deformations driven by local, geometry-changing events that define morphogenesis. Here, we introduce BIOPOINT, a particle-based framework that augments SEM with FEM-like mechanical capabilities by incorporating (1) a deformable, multi-particle nucleus capable of capturing nuclear stress and strain distributions and (2) an explicit ECM layer represented by structured static particles with tunable adhesive potentials. To ensure biological relevance, we calibrate BIOPOINT against single-cell indentation experiments (SKOV3). We then apply this calibrated parameter set, without additional refitting, to two independent scenarios: (i) cell (EC and hMSC) spreading on ECM micropatterns, capturing qualitative coupling between cell and nuclear shape; and (ii) confined migration (MDA-MB-231) through rigid constrictions, qualitatively reproducing the characteristic sequence of nuclear elongation and partial recovery. Differently from previous work, we present a full SEM model that uses heterogeneous particles to model nuclei, cells, and ECM via phase separation. By combining SEM's strength in modeling emergent cell and tissue geometry with a mechanically sound handling of nuclear and ECM interactions, BIOPOINT provides a versatile platform for studying cell behaviors, like shape acquisition and migration through confinement that are relevant to morphogenesis. Implemented within the widely used, open-source LAMMPS ecosystem, BIOPOINT offers an accessible and extensible tool for the community.