Hypoxia versus tissue stiffness in blood vessel disease
Objectives
Hypoxic conditions in blood vessels as well as alterations in tissue stiffness can impact the contractility of smooth muscle cells (SMCs). To resolve mechanobiological effects and tensional states on the single cells level, our team and collaborators will establish a platform and readout modalities for simultaneous assessment of cellular metabolism and mechanobiology. This will include
the implementation of a microfluidic platform for 3D cell culture of vascular cells (SMCs, microvascular endothelial cells), integrating microelectrode arrays (MEA) for electrophysiological stimulation on our FLIM system.
The simulation of healthy and hypoxic conditions in the 3D vascular model and evaluation by FLIM microscopy. FLIM-based oxygen sensing and FLIM-FRET tension sensing of intracellular mechanobiology (e.g. vinculin, nesprin) will be established in correlation to electrophysiological stimulation. Additional analyses will include Calcium and Raman imaging. And
the data generation, establishment of correlative analytical approaches and proof-of-concept studies on pathophysiological in vitro models: an aneurysm (decreased stiffness) and an atherosclerosis scenario (increased stiffness and integration of immune/foam cells) will be established and investigated with the developed tools.
Host Academic Institution: Eberhard Karls University Tübingen