Measuring Changes in Brain Endothelial Barrier Integrity with Two Impedance-based Biosensors in Response to Cancer Cells and Cytokines

Our research focuses on cerebral microvasculature and the blood-brain barrier. Brain endothelial cells regulate molecular flow into the brain. We use impedance-based biosensors to assess the barrier integrity in disease.

With concurrent analysis and multiple treatment variables, we have already established that several cancer cell lines will disrupt the brain endothelium. Importantly, we have established that this is not predominantly mediated by proteases or cytokines but instead could be a function of cancer-related vesicular bodies. We are studying how metastatic cancers disrupt brain endothelial cells, enter the brain, and form secondary tumors.

Using impedance-based biosensors, we explore this interaction to understand cerebral vasculature compromise and disease. Our goal is to identify and block targets to save our brain endothelial cells from disruption. In this protocol, we detail modifications made from five to seven years of experience that will help increase reproducibility and robustness of using both impedance-based technologies.

Advantages and limitations of both systems compared to other technologies are discussed in the manuscript. Using this technology, we can investigate several properties of brain microvascular endothelial cells simultaneously and in real time. We have established that cancer cells and cytokines can disrupt the endothelial barrier.

Next, we will assess if blocking these adhesion molecules or receptors helps to protect the brain endothelial barrier, as measured using these techniques.