Abstract
As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich microdomains, such as caveolae and lipid rafts, which are particularly abundant in the endothelial plasma membrane. We investigated the connection between cholesterol and PIP2 by extracting membrane tethers from bovine aortic endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our results suggest that in BAEC the role of PIP2, as a mediator of membrane-cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the specific role of cholesterol in endothelial cells and may have implications for cholesterol-dependent vascular pathologies.
Highlights
The endothelium of blood vessels is a barrier that maintains the dynamic balance between blood flow and tissue
SEQUESTRATION OF PIP2 DOES NOT AFFECT THE TETHER FORCE IN bovine aortic endothelial cells (BAEC) we compared how membrane-cytoskeleton adhesion is affected by changes in PIP2 in BAEC with PH-PLC-GFP expression
This objective was motivated by earlier findings on the consequences of cholesterol depletion of the plasma membrane, leading, respectively, to the increase and decrease of membrane-cytoskeleton adhesion in BAEC (Sun et al, 2007) and fibroblasts (Kwik et al, 2003)
Summary
The endothelium of blood vessels is a barrier that maintains the dynamic balance between blood flow and tissue. Disruption in endothelial cell function alters the permeability of this barrier and increases the risk of vascular disease, such as atherosclerosis, a potentially fatal abnormality of the circulatory system (Bonetti et al, 2003; Davignon and Ganz, 2004). The opposite result was found in endothelial cells: depletion in membrane cholesterol level strengthened the interaction between the plasma membrane and the cytoskeleton and resulted in the stiffening of endothelial cells (Byfield et al, 2004; Sun et al, 2007)
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