One Cell as a Mixture: Simulations of the Micropipette Aspiration Responses of valvular interstitial cells
Yusuke Sakamoto (ICES, University of Texas at A), Michael Sacks (The University of Texas at Austin)
Mechanics and Physics of Biological Cells
Tue 2:40 - 4:00
Barus-Holley 141
We have developed a model for valvular interstitial cells (VIC) and simulated a micropipette aspiration (MA) experiment. VICs are myofibroblasts characterized by their expression of alpha-smooth muscle actin (alpha-SMA) stress fibers and strong contractile forces. VICs are related to the pathological response of heart valve tissues such as calcification, where the heart valve exhibits abnormal stiffness. Thus, it is important to investigate mechanical properties of the myofibroblasts and their cellular structures as well as the mechanical interactions with their environments. We considered the VIC as a multiphasic continuum mixture that constitutes viscous fluid phase for cytosol and hyperelastic solid phases for different constituents of cytoskeleton. We considered basal (non-oriented) cytoskeleton and oriented alpha-SMA fibers as solid phases. The VIC can be activated due to the contraction of alpha-SMA fibers and deactivated as necessary. Using a mixture model framework, we simulated a cell undergoing a MA experiment, where the cell is aspirated into a tiny pipette by pressure difference in order to estimate mechanical parameters such as cell stiffness, viscosity, creep response, and relaxation response. We also analyzed the VIC microstructure (e.g. the orientation of alpha-SMA fibers), as well as their effects on the whole-cell mechanical properties before and after activation. We used the data obtained by our research group to validate our simulation and calibrate the model parameters. We observed that the more activated the VICs are, the higher the mass density of alpha-SMA phase reaches, and consequently, the stiffer they become during the MA experiments. We also observed that the activated VICs show different mechanical responses to the direction of aspiration. Numerical results from our simulations may play an important role in elucidating how the mechanical properties of VICs cause the pathological response to heart valve tissue.