Effects of biaxial oscillatory shear stress on endothelial cell proliferation and morphology

Abstract

Wall shear stress (WSS) on anchored cells affects their responses, including cell proliferation and morphology. In this study, the effects of the directionality of pulsatile WSS on endothelial cell proliferation and morphology were investigated for cells grown in a Petri dish orbiting on a shaker platform. Time and location dependent WSS was determined by computational fluid dynamics (CFD). At low orbital speed (50 rpm), WSS was shown to be uniform (0-1 dyne/cm(2)) across the bottom of the dish, while at higher orbital speed (100 and 150 rpm), WSS remained fairly uniform near the center and fluctuated significantly (0-9 dyne/cm(2)) near the side walls of the dish. Since WSS on the bottom of the dish is two-dimensional, a new directional oscillatory shear index (DOSI) was developed to quantify the directionality of oscillating shear. DOSI approached zero for biaxial oscillatory shear of equal magnitudes near the center and approached one for uniaxial pulsatile shear near the wall, where large tangential WSS dominated a much smaller radial component. Near the center (low DOSI), more, smaller and less elongated cells grew, whereas larger cells with greater elongation were observed in the more uniaxial oscillatory shear (high DOSI) near the periphery of the dish. Further, cells aligned with the direction of the largest component of shear but were randomly oriented in low magnitude biaxial shear. Statistical analyses of the individual and interacting effects of multiple factors (DOSI, shear magnitudes and orbital speeds) showed that DOSI significantly affected all the responses, indicating that directionality is an important determinant of cellular responses.

Computational modelling of the interaction of shock waves with multiple gas-filled bubbles in a liquid

“…[10][11][12][13][14] The results presented above suggest that forming an AVF via a vein graft onto a straight artery, or onto the inner-curvature of a curved artery, will result in unsteady blood flow patterns and WSS distributions within both the artery (50-60 Hz) and potentially (depending on the venous diameter) within the vein (up to 650 Hz). However, forming an AVF via a vein graft onto the outer-curvature of a curved artery can suppress such unsteadiness.…”

“…In particular regions of low Wall Shear Stress (WSS), highly oscillatory flow, and low Lumen-to-Wall Oxygen Flux (LWOF), leading to wall hypoxia, are all implicated in the initiation of IH. [5][6][7][8][9][10][11][12][13][14][15][16][17] There have been various computational studies of blood flow within AVF and Arterio-Venous Grafts (AVG). In 2003, Loth et al 18 simulated blood flow within idealized AVG and compared results with those obtained in vivo.…”

Suppressing unsteady flow in arterio-venous fistulae

“…[18][19][20][21][22] In this study, we employed a MADS optimisation framework, and CFD simulations, to design a non-planar AVF configuration that suppresses high-frequency flow unsteadiness. Salient aspects of the novel configuration include an anastomosis on the outer curvature of an arterial bend and a looped non-planar venous section with a relatively obtuse anastomotic connection angle.…”

“…5,7,8 Whilst the exact mechanisms underlying development of IH in AVF are unknown, there is considerable evidence to suggest that their inherently unphysiological flow patterns play an important role. 5,8,9 In particular regions of low Wall Shear Stress (WSS), [9][10][11][12][13] low lumen-to-wall oxygen flux (leading to wall hypoxia) [14][15][16][17] and high-frequency flow unsteadiness [18][19][20][21][22] have all been individually implicated in the initiation and development of IH, although it is of course possible that these factors are related, and a combination is responsible.…”

Impedance analysis of endothelial cells undergoing orbital shear stress.

“…Stokes' second problem is extended to the case of an orbiting infinite plate beneath a fluid layer of large height, an equation develops that is identical to Equation (8) (Chakraborty et al, 2012). This analytical solution provides a single wall shear stress value, but the levels of shear that are generated in a dish on an orbital shaker are non-uniform.…”