Effects of divalent cations on cell adhesion between human neutrophil and endothelial ligand VCAM-1: A lattice Boltzmann analysis

It was reported that the circulating blood cells, including neutrophils, were more likely adherent to the curved micro-vessels than the straight ones. Our previous work indicated that the vessel curvature, cell-cell interaction, and wall shear stress variation would greatly affect this preferential adhesion. It was also found that the affinity state of integrins would be influenced by different divalent cations, which provides an opportunity to explore the particular importance of integrins activation in neutrophils adhesion. In this study, we aim at numerically investigating the effects of divalent cations, i.e. Mn2+, Mg2+plus EGTA, and Ca2+, on VLA-4/VCAM-1 adhesion under flow condition. The blood dynamics was carried out by the lattice Boltzmann method (LBM), the neutrophil dynamics was governed by the Newton's law of translation and rotation, and a refined neutrophil adhesive dynamics model that taken into account the effect of wall shear stress gradient on receptor-ligand bonds was applied to solve the VLA-4/VCAM-1 adhesion. The simulation results indicated that the divalent cations significantly influenced neutrophils adhesion under hydrodynamic condition. It was found that the capability of stimulating affinity state of VLA-4 to VCAM-1 was larger in Mg2+plus EGTA than in Ca2+, and largest in the presence of Mn2+. Our results would be helpful to understand the β1-integrin-mediated neutrophils adhesion in real physiological situations.