The Impact of Disturbed Flow Induced Arterial Stiffness on Mechanotransduction in Endothelial Cells
Mentor 1
Mahsa Dabagh
Start Date
10-5-2022 10:00 AM
Description
Atherosclerosis prone regions of the vasculature are exposed to disturbed flow where low and oscillatory wall shear stress affect endothelia cell (EC) functions such as proliferation, apoptosis, migration, permeability, cell alignment and mechanical properties. ECs transduce fluid shear stress resulting from blood flow into intracellular signals whereas the response of subcellular structures to hemodynamic forces play a significant role in vascular health and disease. In this project, we are developing a multiscale, multicomponent model of endothelial cells and intra/inter-cellular organelles to explore how the mechanotransduction in subcellular structures of endothelial cells are influenced under exposure to the disturbed flow. Moreover, we take into account the impact of disturbed flow induced arterial stiffness on mechanotransduction. Our model includes adheres junction, glycocalyx, cytoskeleton, focal adhesions, nucleus, cytosol, and apical layer. In our study, we hypothesize that disturbed flow induced stiffness of the arterial wall will significantly impact the activation of mechanosensors relative to unidirectional flow applied on straight regions of the vasculature. Our results show that changes in the stiffness promotes the activation of mechanosensors in cells exposed to disturbed flow while it doesn’t have same influence in ECs exposed to unidirectional flow. Our study quantifies the forces on integrins, adherence junctions, filaments and other substructures in the range that activate mechanotransduction. Our results provide insight into mechanisms underlying the progress of atherosclerosis and identifies new pathways that may lead to novel therapies to suppress the disease progression.
The Impact of Disturbed Flow Induced Arterial Stiffness on Mechanotransduction in Endothelial Cells
Atherosclerosis prone regions of the vasculature are exposed to disturbed flow where low and oscillatory wall shear stress affect endothelia cell (EC) functions such as proliferation, apoptosis, migration, permeability, cell alignment and mechanical properties. ECs transduce fluid shear stress resulting from blood flow into intracellular signals whereas the response of subcellular structures to hemodynamic forces play a significant role in vascular health and disease. In this project, we are developing a multiscale, multicomponent model of endothelial cells and intra/inter-cellular organelles to explore how the mechanotransduction in subcellular structures of endothelial cells are influenced under exposure to the disturbed flow. Moreover, we take into account the impact of disturbed flow induced arterial stiffness on mechanotransduction. Our model includes adheres junction, glycocalyx, cytoskeleton, focal adhesions, nucleus, cytosol, and apical layer. In our study, we hypothesize that disturbed flow induced stiffness of the arterial wall will significantly impact the activation of mechanosensors relative to unidirectional flow applied on straight regions of the vasculature. Our results show that changes in the stiffness promotes the activation of mechanosensors in cells exposed to disturbed flow while it doesn’t have same influence in ECs exposed to unidirectional flow. Our study quantifies the forces on integrins, adherence junctions, filaments and other substructures in the range that activate mechanotransduction. Our results provide insight into mechanisms underlying the progress of atherosclerosis and identifies new pathways that may lead to novel therapies to suppress the disease progression.
