The full model of micropipette aspiration of cells: A mesoscopic simulation.

Studies on the interaction between cells and micromanipulation tools are necessary to optimize the procedures and improve the developmental potential of cells. The molecular dynamics simulation is not possible for such a large-scale simulation, and the spring-damped viscoelastic models and the constitutive equations of the continuum are usually adopted to model the cells as a whole without consideration of the different properties presented by the heterogeneous subcellular components. In this study, we utilized coarse-grained modeling to develop a subcellular model of suspension cell dynamics and a model of a holding micropipette for the fixation of a suspension cell, and designed a large-scale, accurate mesoscopic simulation environment for specific cell micromanipulation. We established a triangular mesh cell membrane and a uniformly distributed, non-intersecting cytoskeleton network and added polymerization/depolymerization processes to connect the cytoskeleton chains with the membrane and cross-linking proteins. In the cell aspiration model, we adopted the profile of the reversed Poiseuille flow to calibrate the viscosity of the fluid and set the bounce-back condition and the appropriate solid-fluid force coefficient to realize non-slip flow at the boundary. The rheological properties of the cells during micropipette aspiration were further analyzed in the simulation by varying parameters such as the inner diameter of the micropipette, negative pressure, and maximum bond length. The model well reproduced the experimentally observed cell deformation phenomenon at low and high pressures. The dynamic response of the cell elongation observed from the simulation was consistent with that obtained from the analysis of the experimental data collected from a custom-designed micromanipulation system. STATEMENT OF SIGNIFICANCE: In this study, we extended the coarse-grained modeling of cells by developing a relatively large-scale micromanipulation environment consisting of a subcellular cell dynamics model and a fluid flow model for cell aspiration. We simulated cytoskeleton filaments that were uniformly distributed in space via applying Harmonic energy to model cytoskeleton with a high level of fidelity. The shortcoming of the soft repulsion in the solid-fluid interaction in the current simulation technique was solved by implementing the bounce-back boundary and the condition that the total force imposed by the wall particles on the fluid particles was equal to the pressure of the fluid. This work paved the way for understanding the mechanical properties of cells and improving the biological efficacy of micromanipulation.