Mechanobiological cross-talk between epithelia and their immediate environment

The aim of this project area is to study the interaction of epithelia with their surroundings. Epithelia as boundary-forming tissues are interacting with other tissue types. For example, epithelial-endothelial, and epithelial-inflammatory cell cross-talk is at the core of many pulmonary diseases, and epithelial-connective tissue cross-talk determines epithelial pathophysiological differentiation and aging. The involvement of mechanical signals in these processes is poorly understood, despite its high clinical relevance. The goal of this project area is to investigate modes of different types of cross-talk at the single cell and tissue level and to identify the underlying molecular pathways to facilitate tissue engineering and disease management. The selected paradigms address these questions in the respiratory system that is involved in breathing (inspiration and expiration) and gas exchange. Here, mechanical forces act on the topological outside, i.e., ventilation, as well as on the inside via capillaries, i.e., blood flow, all of which are coupled to connective tissue. The new project on the retinal pigment epithelium adds another degree of complexity since it interfaces with connective tissue at its basal side and with neuronal tissue at its apical side.
Interaction of the alveolar epithelium and macrophages under mechanical strain
Institute of Pharmacology and Toxicology, Uniklinik RWTH Aachen
Stefan Uhlig
Principal Investigator
Kathleen Reiss
Junior Supervisor
Sarah Bringezu
Doctoral Researcher
Interaction of the Alveolar Epithelium and Macrophages under Mechanical Strain
Project overview. 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.