Modeling and Validation of Oocyte Mechanical Behavior Using AFM Measurement and Multiphysics Simulation.

Mechanical models are capable of simulating the deformation and stress distribution of oocytes under external forces, thereby providing insights into the underlying mechanisms of intracellular mechanical responses. Interactions with micromanipulation tools involve forces like compression and punction, which are effectively analyzed using principles of solid mechanics. Alternatively, fluid-structure interactions, such as shear stress at fluid junctions or pressure gradients within microchannels, are best described by a multiphase flow model. Developing the two models instead of a single comprehensive model is necessary due to the distinct nature of cell-tool interactions and cell-fluid interactions. In this study, we developed a finite element (FE) model of porcine oocytes that accounts for the viscoelastic properties of the zona pellucida (ZP) and cytoplasm for the case when the oocytes interacted with a micromanipulation tool. Atomic force microscopy (AFM) was employed to measure the Young's modulus and creep behavior of these subcellular components that were incorporated into the FE model. When the oocyte was solely interacting with the fluids, we simulated oocyte deformation in microfluidic channels by modeling the oocyte-culture-medium system as a three-phase flow, considering the non-Newtonian behavior of the oocyte's components. Our results show that the Young's modulus of the ZP and cytoplasm were determined to be 7 kPa and 1.55 kPa, respectively, highlighting the differences in the mechanical properties between these subcomponents. Using the developed layered FE model, we accurately simulated oocyte deformation during their passage through a narrow-necked micropipette, with a deformation error of approximately 5.2% compared to experimental results. Using the three-phase flow model, we effectively simulated oocyte deformation in microfluidic channels under various pressures, validating the model's efficacy through close agreement with experimental observations. This work significantly contributes to assessing oocyte quality and serves as a valuable tool for advancing cell mechanics studies.