Tissue-on-a-chip technologies are more and more important in the investigation of
cellular function and in the development of novel drugs by allowing the direct screening
of substances on human cells. Constituting the inner lining of vessel walls, endothelial
cells are the key players in various physiological processes, moreover, they are the
first to be exposed to most drugs currently used. However, to date, there is still
no appropriate technology for the label-free, real-time and high-throughput monitoring
of endothelial function. To this end, we developed an optical biosensor-based endothelial
label-free biochip (EnLaB) assay that meets all the above requirements. Using our
EnLaB platform, we screened a set of plasma serine proteases as possible endothelial
cell activators, and first identified the endothelial cell activating function of
three important serine proteases – namely kallikrein, C1r and mannan-binding lectin-associated
serine-protease 2 (MASP-2) – and verified these results in well-established functional
assays. EnLaB proved to be an effective tool for revealing novel cellular mechanisms
as well as for the high-throughput screening of various compounds on endothelial cells.
