The intracellular calcium dynamics in a single vascular endothelial cell being squeezed through a narrow microfluidic channel

Biomech Model Mechanobiol. 2021 Feb;20(1):55-67. doi: 10.1007/s10237-020-01368-7. Epub 2020 Jul 24.

Abstract

Revealing the mechanisms underlying the intracellular calcium responses in vascular endothelial cells (VECs) induced by mechanical stimuli contributes to a better understanding for vascular diseases, including hypertension, atherosclerosis, and aneurysm. Combining with experimental measurement and Computational Fluid Dynamics simulation, we developed a mechanobiological model to investigate the intracellular [Ca2+] response in a single VEC being squeezed through narrow microfluidic channel. The time-dependent cellular surface tension dynamics was quantified throughout the squeezing process. In our model, the various Ca2+ signaling pathways activated by mechanical stimulation is fully considered. The simulation results of our model exhibited well agreement with our experimental results. By using the model, we theoretically explored the mechanism of the two-peak intracellular [Ca2+] response in single VEC being squeezed through narrow channel and made some testable predictions for guiding experiment in the future.

Keywords: Cellular surface tension; Intracellular calcium response; Mechanobiology model; Microfluidic experiment; Single cell dynamics; Vascular endothelial cells.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Biomechanical Phenomena
  • Calcium / metabolism*
  • Cell Shape
  • Computer Simulation
  • Homeostasis
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Hydrodynamics
  • Intracellular Space / metabolism*
  • Microfluidics*
  • Models, Biological
  • Reproducibility of Results
  • Surface Tension
  • TRPV Cation Channels / metabolism
  • Time Factors

Substances

  • TRPV Cation Channels
  • Adenosine Triphosphate
  • Calcium