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, Multi-scale simulation of L-selectin–PSGL-1-dependent homotypic leukocyte binding and rupture, Biomechanics and Modeling in Mechanobiology October 2010, Volume 9, Issue 5, pp 613–627 , DOI 10.1007/s10237-010-0201-2

Rights

This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.

Subjects

Cell adhesion
Cell deformation
Immersed boundary method
Monte Carlo simulation
Receptor–ligand bond kinetics
UMBC High Performance Computing Facility (HPCF)

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.