Biology subjects

Chandurkar, M. K.

Publications and source records attributed to Chandurkar, M. K..

2 recordsLinked to original sources

bioRxiv2025

TRPV4 Dominates High Shear-Induced Initial Traction Response and Long-Term Relaxation Over Piezo1

Modulation of endothelial traction is critical for the responses of endothelial cells to fluid shear stress (FSS), which has profound implications for vascular health and atherosclerosis. Previously, we demonstrated that under high FSS, endothelial cells rapidly increase traction forces, followed by relaxation, with traction aligning in the flow direction. In contrast, low shear preconditioning induces a modest short-term increase in traction (<30 min), followed by a secondary long-term (>14 hr) rise, with traction/cells aligning perpendicular to the flow. The upstream mechanosensors driving these responses, however, remain unknown. Here, we sought the roles of Piezo1 and TRPV4 ion channels in shear-induced traction modulation. We report that HUVECs with Piezo1 silencing reduced the initial traction rise in half under high FSS compared to those by WT cells, while not affecting the traction modulation in response to low FSS or traction/cell alignment to the flow direction. Conversely, cells with siTRPV4 fully abrogated the initial traction rise, as well as alignment of traction and cells, in response to both high and low FSS conditions. Dual inhibition of Piezo1 and TRPV4 further impaired both initial and long-term traction under high FSS. Interestingly, dual-inhibited cells displayed larger initial traction responses to low FSS compared to control cells, suggesting the involvement of alternative calcium-independent pathways that become dominant when both ion channels are nonfunctional. Additionally, either ion channel inhibition led to secondary long-term traction increase even under high FSS condition. These findings suggest that while both Piezo1 and TRPV4 channels contribute to shear mechanotransduction, TRPV4 plays more dominant role than Piezo1 in mediating the initial traction rise and sustaining long-term relaxation under high or low shear stress, highlighting their critical and distinct contributions to endothelial mechanotransduction and remodeling.

cell biology↗

bioRxiv2023

Impact of Low Shear Stress Preconditioning on Endothelial Cell Traction and Alignment in Response to High Shear Stress

Within the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction--a measure of cellular tension that plays a crucial role in how endothelial cells respond to mechanical stimuli. By integrating traction force microscopy (TFM) with a custom-built flow chamber, we analyzed how human umbilical vein endothelial cells (HUVECs) adjust their traction in response to shifts from low to high shear stress. We discovered that initial exposure to low FSS prompts a marked increase in traction force, which continues to rise over 10 hours before slowly decreasing. In contrast, immediate exposure to high FSS causes a quick spike in traction followed by a swift reduction, revealing distinct patterns of traction behavior under different shear conditions. Importantly, the direction of traction forces and the resulting cellular alignment under these conditions indicate that the initial shear experience dictates long-term endothelial behavior. Our findings shed light on the critical influence of short-lived low-shear stress experiences in shaping endothelial function, indicating that early exposure to low FSS results in enduring changes in endothelial contractility and alignment, with significant consequences for vascular health and the development of cardiovascular diseases.

cell biology↗