How cholesterol regulates endothelial biomechanics

As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular that of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disrupt...

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Main Authors: Zhongkui eHong, Marius Catalin Staiculescu, Paul eHampel, Irena eLevitan, Gabor eForgacs
Format: Article
Language:English
Published: Frontiers Media S.A. 2012-11-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00426/full
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author Zhongkui eHong
Marius Catalin Staiculescu
Paul eHampel
Irena eLevitan
Gabor eForgacs
Gabor eForgacs
Gabor eForgacs
author_facet Zhongkui eHong
Marius Catalin Staiculescu
Paul eHampel
Irena eLevitan
Gabor eForgacs
Gabor eForgacs
Gabor eForgacs
author_sort Zhongkui eHong
collection DOAJ
description As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular that 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. We provide strong evidence that in endothelial cells the localization and metabolism of PIP2 is controlled by cholesterol. 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.
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spelling doaj.art-bc0a1b100dc2425f82b6d0dc1732281e2022-12-21T19:16:40ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-11-01310.3389/fphys.2012.0042629794How cholesterol regulates endothelial biomechanicsZhongkui eHong0Marius Catalin Staiculescu1Paul eHampel2Irena eLevitan3Gabor eForgacs4Gabor eForgacs5Gabor eForgacs6University of MissouriUniversity of MissouriUniversity of MissouriUniversity of Illinois at ChicagoUniversity of MissouriUniversity of MissouriClarkson UniversityAs endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular that 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. We provide strong evidence that in endothelial cells the localization and metabolism of PIP2 is controlled by cholesterol. 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.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00426/fullCholesterolAtomic Force Microscopy5-bisphosphateMembrane-cytoskeleton adhesionPhosphatidylinositol-4Tether force
spellingShingle Zhongkui eHong
Marius Catalin Staiculescu
Paul eHampel
Irena eLevitan
Gabor eForgacs
Gabor eForgacs
Gabor eForgacs
How cholesterol regulates endothelial biomechanics
Frontiers in Physiology
Cholesterol
Atomic Force Microscopy
5-bisphosphate
Membrane-cytoskeleton adhesion
Phosphatidylinositol-4
Tether force
title How cholesterol regulates endothelial biomechanics
title_full How cholesterol regulates endothelial biomechanics
title_fullStr How cholesterol regulates endothelial biomechanics
title_full_unstemmed How cholesterol regulates endothelial biomechanics
title_short How cholesterol regulates endothelial biomechanics
title_sort how cholesterol regulates endothelial biomechanics
topic Cholesterol
Atomic Force Microscopy
5-bisphosphate
Membrane-cytoskeleton adhesion
Phosphatidylinositol-4
Tether force
url http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00426/full
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