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.

Teams and Projects

Institute of Pharmacology and Toxicology, Uniklinik RWTH Aachen

Interaction of the alveolar epithelium and macrophages under mechanical strain

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.
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

Stefan Jockenhövel
Principal Investigator
Lena Thiebes
Principal Investigator
Hannah Kubiza
Doctoral Researcher
Stress-induced remodeling of an in vitro airway model
Project overview. (A) In vitro tri-culture model of the airway mucosa. PAS and immunohistochemical staining presenting an epithelial layer on top and an underlying fibrin gel seeded with endothelial and supporting cells. (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 are investigated.
Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University Hospital
Institute of Molecular and Cellular Anatomy (MOCA), Uniklinik RWTH Aachen

Dissecting the mechanobiological contribution of Bruch’s membrane for the stability of neural retinal adhesion: a bottom-up approach

Jacopo Di Russo
Principal Investigator
Aleksandra Kozyrina
Associated Doctoral Researcher
The Mechanobiology of Retinal Pigment Epithelium Heterogeneity
Teodora Piskova
Associated Doctoral Researcher
The mechanobiological implication of age-related cell density reduction of retinal pigment epithelium
Felix Reul
Associated Doctoral Researcher
Development of hydrogel-based material to dissect the mechanobiology of RPE in aging
Vasudha Turukverkere Krishnamurthy
Associated Doctoral Researcher
Establishment of an organoid model to study the extracellular matrix contribution to retinal mechanobiology
Project overview. The retina detects light via photoreceptor cells and outer segments (POS), whose homeostasis depends on direct contact with the retinal epithelium (RPE). This epithelium tightly adheres to the Bruch’s membrane (ECM), which defines its function.  Still, the relationship between extracellular matrix biochemistry, physical properties and retinal epithelial mechanobiology has not been addressed. After development, retinal epithelial cells do not proliferate, so the epithelium cannot adapt to the extracellular remodelling that occurs with age (*). This opens the unexplored question of how mechanical forces control the cellular and tissue function of the retina (i.e., retinal mechanobiology) in normal ageing and age-related macular degeneration.