Multi-scale simulation of L-selectin-PSGL-1-dependent homotypic leukocyte binding and rupture

V. K. Gupta, Ihab A. Sraj, K Konstantopoulos, Charles D. Eggleton

Research output: Contribution to journalArticle

Abstract

L-selectin-PSGL-1-mediated polymorphonuclear (PMN) leukocyte homotypic interactions potentiate the extent of PMN recruitment to endothelial sites of inflammation. Cell-cell adhesion is a complex phenomenon involving the interplay of bond kinetics and hydrodynamics. As a first step, a 3-D computational model based on the Immersed Boundary Method is developed to simulate adhesion-detachment of two PMN cells in quiescent conditions. Our simulations predict that the total number of bonds formed is dictated by the number of available receptors (PSGL-1) when ligands (L-selectin) are in excess, while the excess amount of ligands influences the rate of bond formation. Increasing equilibrium bond length results in a higher number of receptor-ligand bonds due to an increased intercellular contact area. On-rate constants determine the rate of bond formation, while off-rates control the average number of bonds by modulating bond lifetimes. Application of an external pulling force leads to time-dependent on- and off-rates and causes bond rupture. Moreover, the time required for bond rupture in response to an external force is inversely proportional to the applied load and decreases with increasing off-rate.

Original languageEnglish (US)
Pages (from-to)613-627
Number of pages15
JournalBiomechanics and Modeling in Mechanobiology
Volume9
Issue number5
DOIs
Publication statusPublished - Oct 2010

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Keywords

  • Cell adhesion
  • Cell deformation
  • Immersed boundary method
  • Monte Carlo simulation
  • Receptor-ligand bond kinetics

ASJC Scopus subject areas

  • Biotechnology
  • Mechanical Engineering
  • Modeling and Simulation

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