Double-tether extraction from human umbilical vein and dermal microvascular endothelial cells

Area of Science:

• Cellular biomechanics
• Immunology
• Biophysics

Background:

• Leukocyte rolling on endothelium under high shear stress involves multiple tethers.
• Endothelial cells are predicted to significantly contribute to simultaneous tethers and rolling stabilization.

Purpose of the Study:

• Quantify double tethers extracted from endothelial cells.
• Determine constitutive parameters for double-tether extraction.
• Investigate the role of endothelial cells in leukocyte rolling stabilization.

Main Methods:

• Micropipette aspiration technique to extract double tethers from endothelial cells.
• Measurement of constitutive parameters: threshold force (F0) and effective viscosity (etaeff).
• Application of a biomechanical model for leukocyte rolling analysis.

Main Results:

• Double-tether extraction parameters (F0, etaeff) are twice those of single tethers.
• Parameters are consistent across human neonatal and adult dermal microvascular, and umbilical vein endothelial cells.
• Parameters are independent of surface receptor type, cytokine stimulation, and cell attachment state.
• A novel correlation predicts cell-substrate separation range (0.01-0.1 microm) during leukocyte rolling.
• Biomechanical model predicts maximum stabilization with double simultaneous tether extraction.

Conclusions:

• Double tethers play a critical role in stabilizing leukocyte rolling under shear stress.
• Endothelial cell properties are robust and consistent in their contribution to tether mechanics.
• The findings provide a quantitative basis for understanding cell adhesion and migration dynamics.