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

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 computation...

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Veröffentlicht in:Biomechanics and modeling in mechanobiology Jg. 9; H. 5; S. 613 - 627
Hauptverfasser: Gupta, V. K., Sraj, Ihab A., Konstantopoulos, Konstantinos, Eggleton, Charles D.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Berlin/Heidelberg Springer-Verlag 01.10.2010
Springer Nature B.V
Schlagworte:
Adhesion
Biological and Medical Physics
Biomechanics
Biomedical Engineering and Bioengineering
Biophysics
Cell adhesion & migration
Computer Simulation
Engineering
Fluid dynamics
Hydrodynamics
Kinetics
L-Selectin - metabolism
Leukocytes
Leukocytes - metabolism
Ligands
Load distribution
Membrane Glycoproteins - metabolism
Monte Carlo simulation
Original Paper
Protein Binding
Receptors, Cell Surface - metabolism
Theoretical and Applied Mechanics
Receptor–ligand bond kinetics
Immersed boundary method
Cell deformation
Monte Carlo simulation
Cell adhesion
ISSN:1617-7959, 1617-7940, 1617-7940
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Zusammenfassung: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.
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ISSN:1617-7959
1617-7940
1617-7940
DOI:10.1007/s10237-010-0201-2