Institute of Molecular Pharmacology, Division of Pharmacology in Inflammation, Uniklinik RWTH Aachen
Role of ion channels and ADAM-family metalloproteinases in mechanobiology
Overview of project B4/C1. (A) The scheme depictsa model for activation of ADAM10/17-mediated shedding events by mechanical activation of Piezo-1 and TRPV4 in HaCaT cells. The photograph below shows the stretch chamber (from R. Merkel; B1) used for mechanical stimulation at left and a scheme of the co-culture system at right. (B) Piezo-1 is activated by Yoda 1 or mechanical stretch and, in turn, enhances ADAM activity. Conversely, ADAM activity is suppressed by knockdown of Piezo-1 (grey bars). (C) Activation of TRPV4 by GSK1016790A or mechanical stretch induces ADAM activity, which is suppressed by the TRPV4 inhibitor HC067047 (grey bar). The project aims to translate these findings into (patho) physiological settings and functions using primary keratinocytes and organotypic skin models.
Institute of Pharmacology and Toxicology, Uniklinik RWTH Aachen
Interaction of the alveolar epithelium and macrophages under mechanical strain
Overview of project C2. Hypothesis: mechanical ventilation causes cyclic strain that hinders the resolution of alveolar inflammation by inhibiting the conversion of pro-inflammatory M1 (red) into anti-inflammatory M2 (blue) macrophages (MΦ) and influences the interaction of macrophages with the epithelium (grey). Model: Differentiated monolayers of hAELVI cells showing typical epithelial cell-matrix and cell-cell junctions after 14 days of maturation in co-culture with primary human MΦ. Approach: uniaxial and equibiaxial cyclic strain on elastomeric substrates.
Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, RWTH Aachen University
Modeling the small airway mucosa in vitro to study mechanobiological effects on tissue remodeling
Background and aim of project C3. (A) In vitro tri-culture model of the airway mucosa. PAS and IHC staining presenting an epithelial layer on top and an underlying fibrin gel seeded with endothelial and supporting cells [64]. (B) Induced differentiation and tissue remodeling of the airway mucosa model after exposure to (patho-)physiological mechanical strain (stretch, pressure, compression, stiffness, wall shear stress) and involvement of mechanosensitive channels/mechano-responsive proteins will be investigated.
Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University Hospital
Dissecting the mechanobiological contribution of Bruch’s membrane for the stability of neural retinal adhesion: a bottom-up approach
Schematic representation of the approaches in C4. In WP1 we will differentiate photoreceptors from human induced pluripotent stem cells (hiPSC) and combine them with hiPSC-RPE to create a 3D co-culture system for studying RPE-photoreceptor interaction. The use of the Anisogel-containing magnetically-responsive, rod-shaped microgels (green rods) will create a scaffold to support the elongation of the photoreceptor outer segments. In WP2 the effect of BrM cues on RPE adhesion strength to the neurosensory retina will be probed using phantom-photoreceptors microgels (blue rods). The RPE microvilli-induced deformation will be visualized by confocal microscopy and analyzed via finite element modeling.