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A Microchip Model Used to Study Vascular Binding

The interactions that take place in the lining of blood vessels throughout the body play important roles in acute and chronic diseases. Leukocytes are recruited to sites of tissue injury or infection. They bind to the cell walls and respond to the local environment during the healing process as well as in chronic disease states.

To study this interaction, investigators at Temple University used an idealized synthetic microvascular network to demonstrate the geometry of the blood vessels influence the flow rate within the vessels and the ability of functionalized particles to bind to the cells lining the vessel wall.

The idealized microvascular network was fabricated as a Polydimethylsiloxane (PDMS) microchip with a 100 µm channel that bifurcates at a 90° angle into two symmetrical daughter channels of 50 µm. The chip was lined with Human Umbilical Vein Endothelial Cells (HUVECs) that were stimulated with Tumor Necrosis Factor-alpha (TNF-α). The design allows for media containing the microparticles to pump through the channels at physiological flow rates while being observed through a microscope.

Intercellular adhesion molecules-1 (ICAM-1) is a cell surface glycoprotein that is expressed on endothelial cells and upregulated by exposure to TNF-α. E-selectin, another cell adhesion molecule is transiently expressed on vascular endothelial cells in response to inflammatory cytokines like IL-1 β and TNF-α.

In this study small (2 µm) fluorescent particles were coated with mixtures of antibodies against ICAM-1 and E-selectin. Different ratios of antibodies and different flow rates were used, and the binding was observed. The particles that were covered with an equal mixture of the antibodies (50:50) showed the highest binding in the idealized system. All of the coated particles bound 3-18 fold higher in the region that included the bifurcation compared with the straight region. The investigators also found the binding in the straight region increased when the shear decreased (at lower flow rates). When the shear changed in the bifurcated regions, the binding did not change significantly.

The Authors’ Conclusion – Adhesion efficiency of functionalized particles is significantly affected by cell-adhesion molecule ratio density as well as geometric features of the vessels.

“Adhesive interaction of functionalized particles and endothelium in idealized microvascular networks.”

Microvascular Research. 2013 Sep; 89:107-14. doi: 10.1016/j.mvr.2013.03.007. Epub 2013 Apr 2

Lamberti G1, Tang Y, Prabhakarpandian B, Wang Y, Pant K, Kiani MF, Wang B.

Department of Mechanical Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122, USA. g.lamberti@temple.edu

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