Abstract
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.
Highlights
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
The Epic BT platform is suitable for the primary screening of the cellular effects of yet uninvestigated substances, as almost any changes in cellular function can affect the refractive index monitored at the bottom surface of the adhered living cells
While the quartz crystal microbalance (QCM)-I measurement relies on a generated standing acoustic plane wave, optical waveguide lightmode spectroscopy (OWLS) employs the evanescent wave that is generated by the excited waveguide modes
Summary
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. Modern technology opened up the possibility to deposit living cells or even reliable tissue models directly on a transducer surface to monitor their behavior in a miniaturized, fast and cost-effective manner These lab-on-a-chip systems are more and more popular in applied biotechnology and their application in basic cell biological research is on the rise[1]. There are several conventional methods suitable for studying cell behavior, these are often low-throughput and time-consuming assays, and usually rely on the detection of labeled molecules, which can per se affect cellular functions, as they may activate unforeseen signaling pathways. To overcome this problem, the introduction of non-invasive label-free technologies is necessary. As ECs are present everywhere in the body in great numbers and are affected by the pathomechanism of several diseases (e.g. atherosclerosis, edematous diseases, sepsis, cancers, etc.), it is important to understand how activated blood components and intravenously administered pharmacological agents affect EC behavior
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