Biomechanics and Modeling in Mechanobiology

, Volume 9, Issue 5, pp 613–627 | Cite as

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

  • V. K. Gupta
  • Ihab A. Sraj
  • Konstantinos Konstantopoulos
  • Charles D. Eggleton
Original Paper

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.

Keywords

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

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • V. K. Gupta
    • 1
  • Ihab A. Sraj
    • 1
  • Konstantinos Konstantopoulos
    • 2
  • Charles D. Eggleton
    • 1
  1. 1.Department of Mechanical EngineeringUniversity of Maryland, Baltimore CountyBaltimoreUSA
  2. 2.Department of Chemical and Biomolecular EngineeringThe John Hopkins UniversityBaltimoreUSA

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