Mechanobiology of differentiation and invasion in 3D cell assemblies

This project area aims to contribute to the understanding of the cross-talk between local mechanical cues and adaptation/differentiation in multilayer epithelia. The selected paradigm is the epidermis, which is by far the most extensive epithelial tissue surrounding the entire outer body surface. It is characterized by the arrangement of tightly-coupled keratinocytes in layer-specific configurations, each with unique differentiation features and mechanobiological properties. To work toward elucidation of mechanical cross-talk mechanisms, novel tools have been and still need to be developed to enable layer-specific analyses. Another focus of this project area is the dysregulation of this balance in human diseases, which are often associated with perturbed neuronal perception resulting in pain and itch. The underlying pathomechanisms of mechanosensation and mechanotransduction are not known.
Role of ion channels and ADAM-family metalloproteinases in mechanobiology
Institute of Molecular Pharmacology, Division of Pharmacology in Inflammation, Uniklinik RWTH Aachen
Andras Ludwig
Principal Investigator
Aaron Babendreyer
Junior Supervisor
Alessa Pabst
Doctoral Researcher
Regulation of the epithelial-endothelial signaling interface by shear stress and substrate stiffness
Project overview. (A) The scheme depicts a 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 the Merkel team) 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.