The Effect of Substrate Stiffness on Endothelial Cell Stiffness and Monolayer Permeability in Response to Inflammation

2021 ◽  
Author(s):  
Rebecca Lownes Urbano
Keyword(s):  
Endothelial Cell ◽  
Substrate Stiffness ◽  
Cell Stiffness ◽  
Monolayer Permeability

Abstract 171: Role of α-Actinin-4-Dependent Endothelial Cell Stiffness in Neutrophil Transmigration

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Peter Hordijk ◽  
Antje Schaefer ◽  
Joost te Riet ◽  
Katje Ritz ◽  
Mark Hoogenboezem ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Feedback Loop ◽  
Leukocyte Adhesion ◽  
Cell Stiffness ◽  
Intercellular Adhesion Molecule ◽  
Ageing Population ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Lining ◽  
Human Disorders

Inflammation is causally linked to many chronic human disorders and constitutes a growing problem in the ageing population. The inflammatory process is driven by interactions of activated leukocytes with the endothelial lining of blood vessels. This requires binding of leukocyte β2-integrins to endothelial ICAM-1 (InterCellular Adhesion Molecule-1), which allows leukocyte adhesion, spreading, crawling and transendothelial migration (TEM). Integrin binding induces ICAM-1 clustering and its consequent association to F-actin which enforces leukocyte adhesion. Here, we analyzed the molecular basis of this positive feedback loop. We show that ICAM-1 clustering promotes its binding to F-actin through distinct complexes with FilaminB, Cortactin and α-Actinin-4. We found that α-Actinin-4 regulates endothelial cell peripheral stiffness, which is sensed by adherent neutrophils and promotes adhesion, spreading, crawling and TEM. Conversely, increasing endothelial cell stiffness stimulates the ICAM-1-α-Actinin-4 interaction. Finally, we found that the endothelial lining of atherosclerotic plaques, which is characterized by increased stiffness and leukocyte infiltration, shows increased expression of α-Actinin-4. These results identify α-Actinin-4-regulated endothelial cell stiffness as a novel pro-inflammatory event that promotes ICAM-1-mediated leukocyte adhesion and TEM.

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