Micro fluidic system for characterization of endothelial permeability and transendothelial leucocyte migration

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The increased permeability of the blood vessel and the transmigration of leucocytes out of the blood through the vessel wall into the inflammed tissue are hallmarks of inflammatory response. In this project a microfluidic chamber with an integrated perforated membrane will be developed for the first time which will be used for real-time and space-resolved characterization of pulmonary endothelial cells permeability and transendothelial migration of leucocytes in a physiological environment. Planar microelectrode arrays will be deposited on both sides of the perforated membrane to characterize the permeability and transmigration behavior locally and quantitatively using impedance spectroscopy measurement techniques. The electrical measurements will be compared with standard fluorescence techniques. The microfluidic chamber will be used to investigate the regulation and function of the surface proteases ADAM 10 and ADAM 17 in endothelial permeability and leukocyte transmigration at the levele og the protease substrates CX3CL1, CXCL16, JAM-A VE-cadherin and ERLR ligands. The system will allow characterizing novel inhibitors against these molecules under physiological conditions in a quantitative and time-effective manner.