Mechanical control of the endothelial barrier

The integrity of the endothelial barrier is controlled by the combined action of chemical and mechanical signaling systems. Permeability-regulating factors signal through small GTPases to regulate the architecture of the cytoskeleton and this has a strong impact on the morphology and stability of VE...

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Bibliographic Details
Published in:Cell and tissue research 2014-03, Vol.355 (3), p.545-555
Main Authors: Oldenburg, Joppe, de Rooij, Johan
Format: Article
Language:English
Subjects:
actin
Actin Cytoskeleton - metabolism
Actomyosin - metabolism
adherens junctions
adhesion
Animals
Antigens, CD - metabolism
Biomedical and Life Sciences
Biomedicine
Cadherins - metabolism
Cell adhesion & migration
Cell Adhesion - physiology
Endothelial Cells - cytology
Endothelial Cells - metabolism
Endothelial Cells - physiology
Endothelium
Endothelium - metabolism
Endothelium - physiology
G proteins
guanosinetriphosphatase
Human Genetics
Humans
mechanical properties
microfilaments
Molecular Medicine
Muscle proteins
Permeability
Proteomics
Review
Signal Transduction
Vascular endothelial growth factor
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Summary:The integrity of the endothelial barrier is controlled by the combined action of chemical and mechanical signaling systems. Permeability-regulating factors signal through small GTPases to regulate the architecture of the cytoskeleton and this has a strong impact on the morphology and stability of VE-cadherin-based cell–cell junctions. The details of how structural and mechanical properties of the actin cytoskeleton influence cell–cell adhesion and how this impacts the dynamic regulation of the endothelial barrier, are beginning to be elucidated. In this review, we discuss the physical and regulatory interactions between the VE-cadherin complex and the actomysoin cytoskeleton, as they are the main determinants of cell–cell adhesion and the mechanical architecture of the cytoskeleton. We discuss, based on recent in vitro data, how a balance between Linear Adherens Junctions, paralleled by cortical actin bundles and Focal Adherens Junctions, connected to radial action bundles, determines endothelial barrier function. We discuss how small GTPases control this balance by regulating the spatial organization and mechanics of actomyosin. We propose a hypothetical model of how biochemical and mechanical signals cooperate locally, at the actomyosin–adhesion interface to open and re-seal the barrier in a rapid and controlled manner.
ISSN:0302-766X
1432-0878
DOI:10.1007/s00441-013-1792-6