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Mimicking a blood vessel to create a ‘bridge’ to better medicine and precision treatment

Nanotechnology has led to better diagnostic techniques and more effective treatments for a variety of illnesses. Tiny devices enable scientists to observe cell activity and deliver drugs to individual cells — a breakthrough that is on the verge of revolutionizing precision medicine for treatment of diseases such as cancer.

One obstacle to fulfilling nanomedicine’s promise is the inability to observe cell to cell interactions at the nanoscale in an environment that closely simulates the dynamic environment inside the body. A micro-fluid environment that mimics blood flow is key to learning how cells become damaged by disease conditions–and how they might recover in response to treatment.

Now a team of researchers at Lehigh University and the University of Pennsylvania has developed a technique to observe cell to cell interaction at the nanoscale under micro-fluid conditions. They have successfully applied the technique to the study of blood vessel inflammation, a condition that sets the stage for heart disease, the number one cause of death in the U.S. and globally. Their findings have been published in Biomicrofluidics.

“We have shown that our technique can be successfully applied to the study of inflammation and are working on a way to similarly observe and intervene in the repair of tumor cells,” said Yaling Liu, Associate Professor of Mechanical Engineering and Mechanics, Bioengineering at Lehigh and a co-author on the study.

Mimicking the dynamic transfer process

Chronic, low-grade inflammation is strongly associated with dysfunctional endothelial cells, which form the inner lining of blood vessels. The appearance of intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells, critical in regulating cell to cell interaction as part of the body’s immune system response, is a sure sign that inflammation and disease are present. Therefore, observing the activation of endothelial cells under disease conditions is essential to understanding how heart disease develops and how to stop it.

The best way to observe these changes is inside the body. However, it is very difficult to do this. Observing the disease in a static cell culture–by removing and growing cells in an artificial environment such as a Petri dish–is limited in its ability to accurately portray the dynamic interactions under blood flow conditions.

In addition to Liu, the team from Lehigh includes Linda Lowe-Krentz, Professor, Biological Sciences; H. Daniel Ou-Yang, Professor, Physics; and Ph.D. student Antony Thomas. They collaborated with Vladimir R. Muzykantov, Professor of Pharmacology at Penn to develop a blood vessel on a chip in order to study the dynamics of ICAM-1 on the surface of endothelial cells activated under disease conditions.

“We were able to mimic and observe the dynamic transfer process–that moment when the intercellular adhesion molecule-1 antibody-coated nanoparticles binds to the cell signaling inflammation upregulation by endothelial cells–on a chip. We were also able to precisely control the flow of fluid,” said Liu. “This reliable and relatively simple method simulates the conditions under which endothelial cells exist in the body, making it possible to observe cellular pathology in real time, and analyze differences in cells’ responses to treatment.”