A new multiphysics model for the physiological responses of vascular endothelial cells to fluid shear stress

Abstract

Vascular endothelial cell (VEC) responds to wall shear stress that has not only spatial variation, but also temporal gradient. To simplify the problem, we first studied how the calcium dynamics of VEC responded to the steady wall shear stress of varying magnitude in a stenosed artery. We then studied how the VEC responded to the periodic shear stress that had temporal variation, as in the pulsatile blood flow. To investigate the multiphysics model of VEC in vitro, we used a mathematical model for intracellular calcium dynamics and a computational fluid dynamics (CFD) method for arterial wall shear stress, either steady or periodic. The CFD results showed that for the steady stenotic flow, the wall shear stress in the recirculating flow was lower than the threshold value, 4 dyne/cm(2), at two particular points: flow separation and flow reattachment. For these subthreshold shear stresses, the peak value of the transient calcium response did not hit the normal saturated level, but reached a reduced magnitude. We investigated the effect of severity of stenosis (SOS) of the stenosed artery. For the pulsatile flow, the so-called shear stress slew rate or the temporal gradient of the first upsurge of the periodic flow was an important factor for the VEC calcium dynamics. The calcium response had a finite range of parameter for SOS and shear stress slew rate in which the calcium response was more sensitive than elsewhere, showing a sigmoid pattern.