Effect of endothelial mechanics on leukocyte guidance and transmigration

Basic data for this project

Description

Localized and tightly controlled leukocyte extravasation is a hallmark of the early inflammatory response. Whereas many cell and protein interactions regulating this process have been well described, recent evidence suggests an active role of endothelial cell mechanics. We propose to quantify mechanical changes of endothelial cells upon mechanical stimulation (substrate stiffness, mechanical stress) and chemical stimulation (TNF-alpha), where an increased stiffness via activation of contractile forces is expected. Intuitively, these additional pulling forces can support the transmigration of leukocytes which will be tested by transmigration assays and a controlled activation of contractility via pharmacologic and optogenetic tools. Combining biophysics, biochemistry and molecular biology we will gain quantitative insights into the forces and the mechanical changes during transmigration and we will study to which extent leukocytes use mechanics to find and mechanically prepare the optimal transmigration site.