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

作者：Gupta V K; Sraj Ihab A; Konstantopoulos Konstantinos; Eggleton Charles D^*

来源：Biomechanics and Modeling in Mechanobiology, 2010, 9(5): 613-627.

DOI：10.1007/s10237-010-0201-2

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

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.

• 出版日期2010-10