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From Surface Protrusion to Tether Extraction: A Mechanistic Model.

Jin-Yu Shao1, Yan Yu1, Sara J Oswald1

  • 1Department of Biomedical Engineering, Washington University, Saint Louis, Missouri 63130, United States.

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|January 9, 2021
PubMed
Summary
This summary is machine-generated.

This study models human leukocyte rolling, revealing how cell surface changes influence tether extraction during blood flow. The findings refine understanding of receptor-cytoskeleton interactions and improve leukocyte emigration simulations.

Keywords:
atomic force microscopycell mechanicsendothelial cellsleukocyte rollingmathematical simulationoptical trap

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Area of Science:

  • Biophysics
  • Cellular Mechanics
  • Immunology

Background:

  • Leukocyte rolling on endothelium is crucial for cell emigration.
  • This process is influenced by shear stress, receptor-ligand interactions, and cell mechanics.
  • Blood flow generates forces that deform leukocytes and endothelial cells.

Purpose of the Study:

  • To develop a two-scale model of cellular deformation under pulling forces.
  • To investigate the transition from surface protrusion to tether extraction.
  • To enhance the accuracy of leukocyte rolling simulations.

Main Methods:

  • Established a two-scale (cellular and molecular) model for cellular deformation.
  • Simulated deformation caused by a point pulling force.
  • Validated simulation results against optical trap and atomic force microscope experiments.

Main Results:

  • Illustrated the transition from surface protrusion to tether extraction, which can be gradual or abrupt.
  • Found that traditional methods for determining force loading rate and protrusional stiffness are reasonable.
  • Demonstrated that crossover force is not solely the rupture force of receptor-cytoskeleton linkage.

Conclusions:

  • The developed model accurately simulates leukocyte deformation and tether extraction.
  • The model offers a more realistic approach to simulating leukocyte rolling.
  • This model can be integrated into existing leukocyte rolling models for improved accuracy.