3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Nanobiosensorics Momentum Group, Institute of Technical Physics and Materials Science, Centre for Energy Research, Konkoly-Thege M. út 29-33, H-1120, Budapest, Hungary.
Sci Rep. 2020 Feb 24;10(1):3303. doi: 10.1038/s41598-020-60158-4.
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.
在细胞功能研究和新型药物开发中，芯片上的组织技术越来越重要，它可以直接在人体细胞上筛选物质。内皮细胞构成血管壁的内层，是各种生理过程中的关键参与者，而且它们是最先接触到目前大多数药物的细胞。然而，迄今为止，仍然没有合适的技术可以用于无标记、实时和高通量监测内皮功能。为此，我们开发了一种基于光学生物传感器的无标记内皮生物芯片（EnLaB）检测方法，该方法满足了所有上述要求。我们使用 EnLaB 平台筛选了一组血浆丝氨酸蛋白酶作为可能的内皮细胞激活剂，并首次鉴定了三种重要的丝氨酸蛋白酶 - 激肽释放酶、C1r 和甘露聚糖结合凝集素相关丝氨酸蛋白酶 2（MASP-2） - 的内皮细胞激活功能，并在成熟的功能检测中验证了这些结果。EnLaB 被证明是一种有效的工具，可以揭示新的细胞机制，并对内皮细胞上的各种化合物进行高通量筛选。
