Flow-Dependent Mass Transfer May Trigger Endothelial Signaling Cascades

It is well known that fluid mechanical forces directly impact endothelial signaling pathways. But while this general observation is clear, less apparent are the underlying mechanisms that initiate these critical signaling processes. This is because fluid mechanical forces can offer a direct mechanical input to possible mechanotransducers as well as alter critical mass transport characteristics (i.e., concentration gradients) of a host of chemical stimuli present in the blood stream. However, it has recently been accepted that mechanotransduction (direct mechanical force input), and not mass transfer, is the fundamental mechanism for many hemodynamic force-modulated endothelial signaling pathways and their downstream gene products. This conclusion has been largely based, indirectly, on accepted criteria that correlate signaling behavior and shear rate and shear stress, relative to changes in viscosity. However, in this work, we investigate the negative control for these criteria. Here we computationally and experimentally subject mass-transfer limited systems, independent of mechanotransduction, to the purported criteria. The results showed that the negative control (mass-transfer limited system) produced the same trends that have been used to identify mechanotransduction-dominant systems. Thus, the widely used viscosity-related shear stress and shear rate criteria are insufficient in determining mechanotransduction-dominant systems. Thus, research should continue to consider the importance of mass transfer in triggering signaling cascades

Transitional Flow in a Cylindrical Flow Chamber for Studies at the Cellular Level

Fluid shear stress is an important regulator of vascular and endothelial cell (EC) functions. Its effect is dependent not only on magnitude but also on flow type. Although laminar flow predominates in the vasculature, transitional flow can occur and is thought to play a role in vascular diseases. While a great deal is known about the mechanisms and signaling cascades through which laminar shear stress regulates cells, little is known on how transitional shear stress regulates cells. To better understand the response of endothelial cells to transitional shear stress, a novel cylindrical flow chamber was designed to expose endothelial cells to a transitional flow environment similar to that found in vivo. The velocity profiles within the transitional flow chamber at Reynolds numbers 2200 and 3000 were measured using laser Doppler anemometry (LDA). At both Reynolds numbers, the velocity profiles are blunt (non-parabolic) with fluctuations larger than 5% of the velocity at the center of the pipe indicating the flows are transitional. Based on near wall velocity measurements and well established data for flow at these Reynolds numbers, the wall shear stress was estimated to be 3–4 and 5–6 dynes/cm(2) for Reynolds number 2200 and 3000, respectively. In contrast to laminar shear stress, no cell alignment was observed under transitional shear stress at both Reynolds numbers. However, transitional shear stress at the higher Reynolds number caused cell elongation similar to that of laminar shear stress at 3 dynes/cm(2). The fluctuating component of the wall shear stress may be responsible for these differences. The transitional flow chamber will facilitate cellular studies to identify the mechanisms through which transitional shear stress alters EC biology, which will assist in the development of vascular therapeutic treatments