Our Motivation: Need for research into the mechanotransduction pathways of vascular endothelial cells. This can help with treatment of cardiovascular disease.

Our Goal: Provide a device that allows researchers to alter the shear stress and tensile strain of cell culture environment.

 

What is a perfusion flow chamber?

– A laboratory device used to study cells under in vivo conditions by subjecting cultured cells to conditions like altered tensile strain or shear stress.

– The device is primarily used to simulate the tensile and shear stresses experienced by vascular wall endothelial cells within the cardiovascular system (2).

Importance:

– Help to understand vascular wall endothelial cells responses to varying mechanical stresses.

-These mechanical stresses are known to elicit to pathological cellular responses which contribute to vascular diseases such as atherosclerosis. (4)

– Our perfusion flow chamber will help researchers to better understand the development of these conditions through direct observation and manipulation of mechanical conditions.

 

(Source 3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211638/pdf/nihms-623399.pdf)

(Source 1: https://www.youtube.com/watch?v=1SvEdg94qUA)

Vascular Endothelial Cell Response:

– Pathological: activate/enhance  pro-inflammatory responses in the presence of a disturbed mechanical environment (2).

– Vascular endothelial cells are responsible for maintaining a proper hemostatic environment. They have respective anticoagulant and antiplatelet mechanisms under normal physiological conditions, which include the release of nitric oxide, prostacyclin. (5) These substances are antithrombotic, and make for a healthy physiological environment.

 

Application:

– The development of atherosclerosis is a chain of events stemming from endothelial dysfunction. (5)

– Development of atherosclerosis is further considered to be a primary cause of cardiovascular diseases.

 

Current Models:

Shearing-Stretching Device

 

Source: Reference 2

This current design is a cell culture on a flexible membrane. Under the center of the membrane is a cylinder allowing for the outside of the membrane to be pulled. This pulling causes tensile strain on the cells. The pressure comes from a vacuum seal under the membrane. On top of the cell culture there are rotating cones that produce shearing force. The limitations to this model is the fact that since it is a closed system the activation products build up in cell culture.

Parallel Plate Flow Chamber

Source: Reference 6

An alternate design utilizes the design of an open system to supply shear stress to the cell culture. The fluid enters from a source and passes once through the reservoir containing the cell culture. The associated limitations are that the cells must be removed for examination which could lead to complications, and that most of the applied force is shear stress rather than tensile strain.

 

 

References:

(1) Lippy, A. (2016, August 23). Acute Inflammation- Educational 3D Animation. Retrieved from https://www.youtube.com/watch?v=1SvEdg94qUA .

(2) Meza, Daphne, et al. (2016, March 1). A Shearing-Stretching Device That Can Apply Physiological Fluid Shear Stress and Cyclic Stretch Concurrently to Endothelial Cells. Retrieved from

https://asmedigitalcollection.asme.org/biomechanical/article-abstract/138/3/031007/370473/A-Shearing-Stretching-Device-That-Can-Apply?redirectedFrom=fulltext

(3) Turbell, John, et. al. “Fluid Mechanics, Arterial Disease, and Gene Expression.” Annu Rev Fluid Mech. (2014): 26. Web.<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211638/pdf/nihms-623399.pdf>.

(4) Davies, Peter, et al. (2009). Hemodynamic Shear Stress and the Endothelium in Cardiovascular Pathphysiology. Nat Clin Pract Cardiovasc Med. Web. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851404/pdf/nihms187584.pdf

(5) Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Blood Vessels and Endothelial Cells. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26848/).

(6) Jutila, Mark A, et al. “Measurement of Neutrophil Adhesion under Conditions Mimicking Blood Flow.” Methods in Molecular Biology (Clifton, N.J.), U.S. National Library of Medicine, 2007, https://www.ncbi.nlm.nih.gov/pubmed/18453116.