Bioactivity and cellular uptake of distinct nanoparticles in human endothelial cells

纳米颗粒（NPs）在环境中无处不在，随着工业的大量生产，它们的数量不断增加。这导致人体持续暴露于NP。由于我们不能通过气道系统、胃肠道和皮肤逃脱NP摄取，因此穿过这些生理屏障的NP将进入被内皮细胞（EC）覆盖的血液和淋巴管系统。这些细胞在控制炎症、凝血、血流和血压方面发挥着重要作用。因此，EC活性的任何干扰都可能导致炎症或凝血状况，对人类健康产生重大影响。我们团队的跨学科方法使我们能够分析NP（由Reller教授（资源战略）设计）对人类EC（Hilger教授（医学））的生物活性，使用单个NP跟踪显微镜（Bräuchle教授（生物物理化学）），声学驱动微流体和脂质膜作为细胞膜的简单模型（Wixforth教授（纳米技术））的组合强度。通过直接在芯片上的微流体实验室上生长EC来模拟我们人工血管的生理条件，我们将在短期和长期时间尺度（分钟到几天）上研究NP对人类EC的生物活性和毒性。我们的微流控系统的光学可及性和小尺寸使我们能够通过凋亡标记物、细胞内信号传导以及促炎和凝固蛋白释放通过EC的荧光、炎症反应和毒性来检测生物活性。此外，可以通过应用由NP跟踪显微镜和控制NP-细胞碰撞速率和局部NP浓度的微流控反应器组成的混合技术来详细监测摄取速率和途径。监测NP与脂质膜的相互作用是从物理角度理解NP对细胞膜的影响的有价值的工具。所有获得的结果将与NP类型和大小相关。

Nanoparticles (NPs) are omnipresent in the environment and their quantity increases constantly as they are produced in large numbers by the industry. This leads to a constant NP exposure of the human body. As we are not able to escape NP uptake via the airway system, gastro-intestinal tract and skin, NPs crossing these physiological barriers will enter the blood and lymphatic vessel system which is covered by endothelial cells (EC). These cells play an essential role concerning the control of inflammation, coagulation, blood flow and blood pressure. Therefore, any disturbance of EC activity may lead to inflammatory or coagulatory conditions with great impact on human health. The interdisciplinary approach of our team allows us to analyze the bioactivity of NPs (designed by Prof. Reller (Resource Strategy)) on human EC (Prof. Hilger (medicine)) using the combined strength of single NP tracing microscopy (Prof. Bräuchle (biophysical chemistry)), acoustically driven microfluidics and lipid membranes as simple models for cell membranes (Prof. Wixforth (nanotechnology)). Mimicking the physiological conditions of our artificial blood vessels by growing EC directly on a microfluidic lab on a chip, we will study the bioactivity and toxicity of NPs on human EC on short and long time scales (minutes to days). The optical accessibility and small size of our microfluidic system enables us to detect bioactivity by means of fluorescence, inflammatory response and toxicity of ECs by apoptotic markers, intracellular signalling and proinflammatory and coagulatory protein release. In addition uptake rates and pathways can be monitored in detail by applying the hybrid technique composed of NP tracking microscopy and the microfluidic reactor which controls NP-cell collision rate and local NP concentration. Monitoring the interactions of NPs with lipid membranes is a valuable tool to understand the impact of NPs on the cell membrane from a physical point of view. All gained results will be correlated to NP type and size.