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Mapping endothelial cell responses to pulsatile shear stress using a pulse-on-chip platform

Mapping endothelial cell responses to pulsatile shear stress using a pulse-on-chip platform

Introduction | modeling atherosclerosis
The fluid wall shear stress (WSS) driven by pulsatile blood flow is a determining factor for the development of atherosclerosis.1 In physiological circumstances, WSS acts simultaneously on endothelial cells (EC) lining blood vessels modulating their biological activity. The height of the WSS varies with the geometry of blood vessels, determining whether a region is prone to atherosclerosis.2,3 Mimicking hemodynamic conditions in pulsatile blood flow is essential to understanding cardiovascular diseases.

Mapping endothelial cellFigure 1. Left. EC morphology in response to WSS; Right. Disturbed flow causes local decreases in shear stress (in red) as a result of geometry. (Adpted from Hahn & Schwartz, 2009)

Cells sense the WSS with their mechanoreceptors and respond by activation of various signaling pathways. Known pathways such as Wnt/ β-catenin, notch signaling, hippo-YAP/TAZ are reported to specifically cause the development of atherosclerosis.4,5

Project | determining the effect of shear stress on endothelial cells
This project aims to map the activation of multiple mechanotransductory pathways that are involved in atherosclerosis in endothelial cells at different levels of WSS and to discover an obvious pattern. We hypothesize that there is a relation between the level of shear stress on endothelial cells and the activation of the mechanosensitive pathways such as Wnt/β-catenin, Notch signaling, and/or YAP/TAZ.

Mapping endothelial cell1Figure 2. Cross section of the microfluidic chip. Magnetically actuated hydrogel valve will open and close to make flow pulsatile, like physiological blood flow. The pulsatile flow will result in dynamic wall shear stress that is experienced by cells in the cell channel.

We are currently developing a pulse-on-chip platform where the cells can experience pulsatile flow unlike what they can experience in well plate-based platforms.

Collaboration | In this project, we collaborate with Prof. Carlijn Bouten in the STEM group.

Goal | milestones and achievements
The goals of this project are:

  • To build a microfluidic system that is capable of generating pulsatile flow on cells in a physiologically relevant manner.
  • Validate the system using endothelial cells to identify the effect of the aforementioned pathways.


  1. Dhawan, Saurabh S., et al. "Shear stress and plaque development." Expert Rev. Cardiovasc. Ther. 8(4): 545-556 (2010).
  2. Topper, J. N., et al. "Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype." Mol. Med. Today, 4310: 40– 46 (1999).
  3. Mohammed, M., et al. Studying the Response of Aortic Endothelial Cells under Pulsatile Flow Using a Compact Microfluidic System. Anal. Chem. 91: 12077–12084 (2019).
  4. Gimbrone, M. J. A., et al. Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc. Pathol. 22: 9–15 (2013).
  5. Souilhol, C., et al. Endothelial responses to shear stress in atherosclerosis: a novel role for developmental genes. Nat. Rev. Cardiol. 17(1): 52-63 (2019).