Abstract

In the emerging field of 3D bioprinting, cell damage due to large deformations is considered a main cause for cell death and loss of functionality inside the printed construct. Those deformations, in turn, strongly depend on the mechano-elastic response of the cell to the hydrodynamic stresses experienced during printing. In this work, we present a numerical model to simulate the deformation of biological cells in arbitrary three-dimensional flows. We consider cells as an elastic continuum according to the hyperelastic Mooney–Rivlin model. We then employ force calculations on a tetrahedralized volume mesh. To calibrate our model, we perform a series of FluidFM^{{textregistered }} compression experiments with REF52 cells demonstrating that all three parameters of the Mooney–Rivlin model are required for a good description of the experimental data at very large deformations up to 80%. In addition, we validate the model by comparing to previous AFM experiments on bovine endothelial cells and artificial hydrogel particles. To investigate cell deformation in flow, we incorporate our model into Lattice Boltzmann simulations via an Immersed-Boundary algorithm. In linear shear flows, our model shows excellent agreement with analytical calculations and previous simulation data.

Highlights

  • The dynamic behavior of flowing cells is central to the functioning of organisms and forms the base for a variety of biomedical applications

  • We presented a simple but accurate numerical model for cells and other microscopic particles for the use in computational fluid-particle dynamics simulations

  • The elastic behavior of the cells is modeled by applying Mooney–Rivlin strain energy calculations on a uniformly tetrahedralized spherical mesh

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Summary

Introduction

The dynamic behavior of flowing cells is central to the functioning of organisms and forms the base for a variety of biomedical applications. Our approach is less computationally demanding than conventional finite-element methods which usually require large matrix operations It is extensible and allows, e.g., the inclusion of a cell nucleus by the choice of different elastic moduli for different parts of the volume. In a plane Couette (linear shear) flow, we investigate the shear stress dependency of single cell deformation, which we compare to the average cell deformation in suspensions with higher volume fractions and show that our results in the neo-Hookean limit are in accordance with earlier elastic cell models (Gao et al 2011; Rosti et al 2018; Saadat et al 2018)

Theory
Calculation of elastic forces
Interpolation of the displacement field
Taylor deformation parameter
Comparison of the numerical model to FluidFMR measurements on REF52 cells
Simulation setup
Comparison of our numerical model to other micromechanical setups
Validation with axisymmetric simulations
Validation with AFM experiments
Application in shear flow
Multiple cell simulations
Conclusion
Findings
Compliance with ethical standards
Full Text
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