Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors.
Biomech Model Mechanobiol
; 18(1): 5-16, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30088112
ABSTRACT
Recent experimental evidence points to the possibility that cell surface-associated caveolae may participate in mechanotransduction. The particular shape of caveolae suggests that these structures serve to prevent exposure of putative mechanosensors residing within these membrane invaginations to shear stresses at magnitudes associated with initiation of cell signaling. Accordingly, we numerically analyzed the fluid flow in and around caveolae using the equation of motion for flow of plasma at low Reynolds numbers and assuming no slip-condition on the membrane. The plasma velocity inside a typical caveola and the shear stress acting on its membrane are markedly reduced compared to the outside membrane. Computation of the diffusion field in the vicinity of a caveola under flow, however, revealed a rapid equilibration of agonist concentration in the fluid inside a caveola with the outside plasma. Western blots and immunocytochemistry support the role of caveolae as shear stress shelters for putative membrane-bound mechanoreceptors such as flk-1. Our results, therefore, suggest that caveolae serve to reduce the fluid shear stress acting on receptors in their interior, while allowing rapid diffusion of ligands into the interior. This mechanism may permit differential control of flow and ligand activation of flk-1 receptor in the presence of ligands.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reologia
/
Estresse Mecânico
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Membrana Celular
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Receptores de Superfície Celular
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Cavéolas
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Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Células Endoteliais
Limite:
Animals
Idioma:
En
Revista:
Biomech Model Mechanobiol
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos