Pulsatile Shear Stress in Endothelial Mechanobiology

Endothelial cells (ECs) line the luminal surface of blood vessels. They are exposed to, and differentially respond to, hemodynamic forces depending on their anatomic location. Pulsatile shear stress (PS) is defined by laminar flow and is predominantly located in straight vascular regions, while disturbed or oscillatory shear stress (OS) is localized to branch points and bifurcations. Such flow patterns have become a central focus of vascular diseases, such as atherosclerosis, because the focal distribution of endothelial dysfunction corresponds to regions exposed to OS, whereas endothelial homeostasis is maintained in regions defined by PS. Mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus, such as PS or OS, into electrochemical activity, such as activation of signaling pathways and transcriptional regulation

Deciphering the mechanotransduction events that occur in ECs in response to differential flow patterns has required the innovation of multidisciplinary approaches in both in vitro and in vivo systems. The results from these studies have identified a multitude of shear stress-regulated molecular networks in the endothelium that are implicated in health and disease [1]. This article will discuss how you can use the Cellix pumps for Pulsatile Shear Stress experiments in Endothelial Mechanobiology.

The role of Endothelial Mechanobiology for improvement of human health

A paradigm shift in the field of mechanotransduction has been seen by resolving mechanisms demonstrating the active role ECs play in the pathogenesis of vascular-related disorders, such as atherosclerosis. These advancements were enabled in part through the application of innovative approaches that amalgamate disciplinary boundaries from cellular and molecular levels to translational vascular medicine that pave the way for new vascular biology studies in the whole organism, [1]. Responding to local mechanical cues that synergize with stimulations originating throughout the organism, endothelial cells orchestrate cellular responses in vascular and subvascular regions that are implicated in a number of diseases such as pulmonary hypertension, Alzheimer's disease, vascular dementia, and pancreatic cancer, [2, 3, 4, 5, 6].

New advances in data science, automation of data analytic techniques, and enhanced data storage and sharing technologies are enhancing the ability to translate conclusions drawn from rodent models into humans. These new fields improve our ability to conduct studies that integrate diverse scientific expertise. These growing multidisciplinary, collaborative environments will continue to transform the field of endothelial mechanobiology into an era involving the generation and interpretation of an array of unbiased biological datasets that provide a systems view of EC function in the entire organism. As the scientific community explores available data and finds new innovative approaches to explore endothelial mechanobiology, this evolving field will continue to improve human health, [1].

How the Cellix pumps work for Pulsatile Shear Stress experiments in Endothelial Mechanobiology

Often in experiments studying the endothelium, imprecise peristaltic or conventional syringe pumps are used, which can produce inaccurate results that slow down research time. Our ExiGo pump provides the precision and versatility needed for these research applications.

The following diagram shows how the ExiGo pump is used in an experiment, in conjunction with a microfluidics chip:

First, a syringe is inserted into the ExiGo pump. These syringes can range from 100 micro litres to 5 millilitres.
The ExiGo pump can then be controlled by our SmartFlo software. This allows you to automate your flow process with custom shear stress and flow rate patterns.
Next, the sample in the syringe is pumped through a Flow Sensor, which monitors the shear stress and flow rate patterns, and adjusts them to your use case.
The sample makes its way through the microfluidics chip, where the sample can interact over the endothelial cells with your flow profile, for example, in an oscillatory flow pattern.
A reservoir vessel is connected to collect the output of the microfluidics chip.
Once the syringe is empty, the sample fluid can be replenished from a reservoir, using a pump manifold connected to a culture media vessel. This allows you to extend the capacity of the syringe and run the experiment continuously for however long is necessary.

This setup increases the efficiency and accuracy of your endothelial cell experiments.

If you’d like to learn more about our microfluidics solutions, check out our website at here contact us at info@wearecellix.com.

References

Minge He, Marcy Martin, Tracy Marin, Zhen Chen, Brendan Gongol. Endothelial mechanobiology. APL Bioengineering 4, 010904 (2020); https://doi.org/10.1063/1.5129563
J. Zhang, J. Dong, M. Martin, M. He, B. Gongol, T. L. Marin, L. Chen, X. Shi, Y. Yin, F. Shang, Y. Wu, H. Y. Huang, J. Zhang, Y. Zhang, J. Kang, E. A. Moya, H. D. Huang, F. L. Powell, Z. Chen, P. A. Thistlethwaite, Z. Y. Yuan, and J. Y. Shyy, “ AMP-activated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension,” Am. J. Respir. Crit. Care Med. 198, 509–520 (2018). https://doi.org/10.1164/rccm.201712-2570OC
R. J. Kelleher and R. L. Soiza, “ Evidence of endothelial dysfunction in the development of Alzheimer's disease: Is Alzheimer's a vascular disorder?,” Am. J. Cardiovasc. Dis. 3, 197–226 (2013).
F. Wang, Y. Cao, L. Ma, H. Pei, W. D. Rausch, and H. Li, “ Dysfunction of cerebrovascular endothelial cells: Prelude to vascular dementia,” Front. Aging Neurosci. 10, 376 (2018). https://doi.org/10.3389/fnagi.2018.00376
J. Luo, P. Guo, K. Matsuda, N. Truong, A. Lee, C. Chun, S. Y. Cheng, and M. Korc, “ Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo,” Int. J. Cancer 92, 361–369 (2001). https://doi.org/10.1002/ijc.1202
A. McGuigan, P. Kelly, R. C. Turkington, C. Jones, H. G. Coleman, and R. S. McCain, “ Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes,” World J. Gastroenterol. 24, 4846–4861 (2018). https://doi.org/10.3748/wjg.v24.i43.4846

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