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.
Mechanical triggers in painful skin diseases
Institute of Neurophysiology, Uniklinik RWTH Aachen
Angelika Lampert
Principal Investigator
Ramona Hohnen
Associated Postdoctoral Researcher
Fiona Roll
Doctoral Researcher
Modulation of sensory nerve excitability by a pain-linked variant in Nav1.9 and keratinocytes under mechanical stress
Marlene Menke
Doctoral Researcher
Thesis Title
Project overview. (A) Diseases selected for studies on mechanically-induced pain. (B) Neurites from mouse dorsal root ganglions (DRGs) are are guided in the vertical direction by microgels in an Anisogel (left). Presence of peripheral neuronal stem cells (green) improves overall DRG neurite growth (cyan; right). (C) depicts the different components used for keratinocyte-neuron co-cultures: (Left) Fibronectin coating (red) covalently linked to the top of a 3D PEG-based hydrogel. (Middle) Keratinocytes forming a continuous monolayer (green) on top of the fibronectin coated PEG gel. (Right) Co-culture of a mouse DRG (red) with keratinocyte (green)/fibronectin layers on top. Note the neurites approaching the epithelial monolayer. (D) Schemes of methods used to apply mechanical stimulation. (E) shows patch-clamped neurons cultured on top of a patterned light-responsive hydrogel at left. A change in membrane potential is detected when neurites are mechanically stimulated by light-actuated hydrogel deformation pulse (middle). Co-culture of neurons with keratinocytes on top of these hydrogels shows the formation of contact points between neurites and keratinocytes (right).