Document Type
Article
Publication Date
2-11-2025
Department
Department of Biomedical Engineering; Department of Mechanical Engineering-Engineering Mechanics; Department of Biological Sciences; Health Research Institute
Abstract
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 (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.
Publication Title
bioRxiv : the preprint server for biology
Recommended Citation
Chandurkar, M.,
Yang, M.,
Rostami, M.,
&
Han, S.
(2025).
TRPV4 Dominates High Shear-Induced Initial Traction Response and Long-Term Relaxation Over Piezo1.
bioRxiv : the preprint server for biology.
http://doi.org/10.1101/2025.02.10.637570
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p2/1471
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Version
Publisher's PDF
Included in
Biology Commons, Biomedical Engineering and Bioengineering Commons, Mechanical Engineering Commons
Publisher's Statement
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. Publisher’s version of record: https://doi.org/10.1101/2025.02.10.637570