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Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors

  • H. Shin
  • J. H. Haga
  • T. Kosawada
  • K. Kimura
  • Y. S. Li
  • S. Chien
  • G. W. Schmid-Schönbein
Original Paper
  • 22 Downloads

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.

Keywords

Caveolin Vascular endothelial growth factor receptor Membrane mechanics Flow analysis Diffusion analysis Finite element analysis Shear stress 

Notes

Funding

This study was funded by JSPS Grant-in-Aid for Scientific Research, No. (B)12450093, 14655089, (B)15360119 and NIH Program Project Grant HL 43026.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Bioengineering and Institute of Engineering in MedicineUniversity of California San DiegoLa JollaUSA
  2. 2.F. Joseph Halcomb III, M.D. Department of Biomedical EngineeringUniversity of KentuckyLexingtonUSA
  3. 3.Department of Mechanical Systems EngineeringYamagata UniversityYonezawaJapan

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