Cell Spheroid Micromechanics under Large Deformations

This study establishes a new mechanical framework for quantifying large-strain compression behavior in 3D cell spheroids, advancing micromechanical characterization at physiologically relevant deformations. Human primary cardiac fibroblast spheroids were compressed up to 50% strain using parallel-plate microcompression and analyzed via a nonlinear hyperelastic contact model (extended Tatara). The study compared classical Hertzian, Ding, and Tatara models against the extended formulation, revealing that traditional Hertz-based models significantly overestimate apparent moduli under large deformations. The extended Tatara model, incorporating Mooney–Rivlin hyperelasticity and lateral expansion effects, achieved superior fits (R² ≈ 0.99) across 10–50% strain, providing more accurate apparent modulus and Poisson’s ratio estimates (≈0.43). These findings clarify nonlinear deformation mechanisms in soft biological aggregates, supporting precise biomechanical modeling of cardiac fibrosis progression and tissue remodeling.