Bioactivity and cellular uptake of distinct nanoparticles in human endothelial cells

• Antragstellerinnen / Antragsteller: Professor Dr. Christoph Bräuchle; Professorin Dr. Ingrid Hilger; Professor Dr. Armin Reller; Professor Dr. Achim Wixforth
• Fachliche Zuordnung: Experimentelle Physik der kondensierten Materie ; Biophysik ; Festkörper- und Oberflächenchemie, Materialsynthese ; Pharmakologie ; Physikalische Chemie von Molekülen, Flüssigkeiten und Grenzflächen, Biophysikalische Chemie
• Förderung: Förderung von 2008 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 57464392

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.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1313: Biological Responses to Nanoscale Particles (Bio-Nano-Responses)