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.
Dissecting the mechanobiological contribution of Bruch’s membrane for the stability of neural retinal adhesion: a bottom-up approach
Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University Hospital
Institute of Molecular and Cellular Anatomy (MOCA), Uniklinik RWTH Aachen
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
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.