Microscale consolidation analysis of relaxation behavior of single living chondrocytes subjected to varying strain-rates

Abstract

AFM Strain-rate dependent response a b s t r a c t Besides the elastic stiffness, the relaxation behavior of single living cells is also of interest of various researchers when studying cell mechanics. It is hypothesized that the relaxation response of the cells is governed by both intrinsic viscoelasticity of the solid phase and fluid-solid interactions mechanisms. There are a number of mechanical models have been developed to investigate the relaxation behavior of single cells. However, there is lack of model enable to accurately capture both of the mechanisms. Therefore, in this study, the porohyperelastic (PHE) model, which is an extension of the consolidation theory, combined with inverse Finite Element Analysis (FEA) technique was used at the first time to investigate the relaxation response of living chondrocytes. This model was also utilized to study the dependence of relaxation behavior of the cells on strain-rates. The stressrelaxation experiments under the various strain-rates were conducted with the Atomic Force Microscopy (AFM). The results have demonstrated that the PHE model could effectively capture the stress-relaxation behavior of the living chondrocytes, especially at intermediate to high strain-rates. Although this model gave some errors at lower strain-rates, its performance was acceptable. Therefore, the PHE model is properly a promising model for single cell mechanics studies. Moreover, it has been found that the hydraulic permeability of living chondrocytes reduced with decreasing of strain-rates. It might be due to the intracellular fluid volume fraction and the fluid pore pressure gradients of chondrocytes were higher when higher strain-rates applied.

Investigation of Cell-Substrate Adhesion Properties of Living Chondrocyte by Measuring Adhesive Shear Force and Detachment Using AFM and Inverse FEA

“…In our previous studies21303133, it has been revealed that PHE model is a powerful and potential model to simulate single cell mechanical behavior since it can account for cellular solid-fluid interaction. Therefore, this model will be used in this study to simulate time-dependent adhesion behavior of single chondrocytes.…”

“…Therefore, this model will be used in this study to simulate time-dependent adhesion behavior of single chondrocytes. AFM biomechanical testing with different strain-rates will be conducted since this is an effective technique to identify all the material constants for PHE model213031. In this study, the mechanical responses of chondrocytes subjected to three different strain-rates (i.e.…”

“…This model gives more accurate and reliable results compared to solid models as it is well-known that cells comprise of both solid and fluid phases. In addition, this model has been proven to precisely simulate cellular mechanical properties and responses subjected to various environmental conditions21303142. The simulation results of Mises solid stress and pore fluid pressure distributions of chondrocytes at different seeding time are shown in Figure S-2 and Video V-4 to V-9 in Supplementary Material.…”

“…Among them, consolidation theory, which was then extended to the PHE material law, has showed its potential in cell mechanics studies213031. This PHE model has been used in several engineering fields such as mechanics46 and biomechanics47484950, with the theoretical details presented by several authors4751525354.…”

“…The FEA model coupled with the porohyperelastic (PHE) mechanical model3031 and a cohesive zone formulation32 will be used to explore the mechanism underlying the adhesive behaviour of single living cells. The PHE model is used in this study because it has been proven to be a powerful model to investigate the fluid-solid interaction within the cells303133. The model proposed in this study is the first one to integrate multi-phase model with cohesive zone formulation to investigate the adhesive properties of chondrocytes.…”