Abstract
Mechanically characterizing biological tissues at the microscale helps to better link microscalebiomechanics to mechanobiology but also contributes to the mechanistic understanding of diseasemechanobiology. Cell spheroids (CSs) are state-of-the-art in vitro three-dimensional cell culturesallowing for the synthesis of microtissue models into sphere-like geometry. Such a geometry isattractive for micromechanical assessment via parallel-plate compression, since only minimal andnondestructive sample preparation is required to conduct such tests. However, appropriate dataanalysis and interpretation methods are mostly lacking. Current approaches, relying on Hertziantheory and its modifications, are inadequate for capturing large deformations observed in CSs uponcompression. Here, we utilized the extended Tatara model, incorporating hyperelasticity and nonlinearboundary effects, to investigate CS mechanics. To evaluate the effectiveness of the model, wecompared results to Hertz, Ding, and simple Tatara models. The extended Tatara model demonstratedsuperior accuracy, enabling mechanical analysis of CSs under compression of up to 50% strain.Estimating the apparent Poisson’s ratio via image segmentation and shape analysis helped refine thecalculated apparent modulus. This work establishes a robust analytical framework that will, in thefuture, help advance our understanding of cardiac fibrosis progression and support the development oftherapeutic strategies using patient-derived CSs as test models.