Computational Modelling of Mechanically Induced Cellular Signalling in Endothelial to Mesenchymal Transition
Atherosclerosis is a chronic, systemic inflammatory disease and remains the leading cause of mortality and morbidity worldwide. While regions of altered wall shear stress have long been associated with atheroprone areas, other mechanical factors such as stiffness, stretch, and pressure have received comparatively little attention. This project investigates the role of mechanical stimuli in regulating Endothelial to Mesenchymal Transition (EndMT), a process that plays a critical role in the onset and progression of atherosclerosis.
EndMT is a cellular transformation in which endothelial cells lose their specific phenotype and acquire mesenchymal characteristics. We hypothesize that EndMT is regulated by the local biophysical niche and the associated cellular signalling pathways. Although mechanical stimuli are known to activate signalling cascades, complexity arises from the simultaneous presence of multiple, interacting mechanical and biochemical inputs. The crosstalk between pathways makes it difficult to isolate the drivers of specific cellular phenotypes.
To address this challenge, we are developing a computational framework that simulates the signalling dynamics underlying EndMT. This approach allows us to identify the most relevant pathways, test hypotheses, and understand how specific mechanical environments shape cellular behaviour. The model is continuously refined and validated through experiments in the laboratory.
Project Lead
Flurina Schuhmacher