Adhesive dynamics simulations of the shear threshold effect for leukocytes

Prior research has shown that mechanical forces influence the dissociation of selectin bonds. These bonds are central to leukocyte rolling on endothelial surfaces. However, the exact relationship between bond mechanics and cell rolling behavior remains unclear. Experimental data suggest that some bonds behave as catch bonds at low force and slip bonds at high force. This catch-slip behavior is thought to affect rolling dynamics under shear stress. The shear threshold effect has been observed in experiments but its molecular basis is not fully understood. Existing models have not yet captured the full complexity of how bond mechanics influence rolling velocity. This gap motivated the development of adhesive dynamics simulations to explore the effect of catch-slip bonds on rolling behavior. The need for a computational approach to model these interactions is clear.

This study aimed to investigate the shear threshold effect in leukocyte rolling using adhesive dynamics simulations. The goal was to determine whether catch-slip bond behavior can explain the observed threshold in rolling velocity. The researchers focused on L-selectin, a key player in leukocyte adhesion. They incorporated a catch-slip dissociation model into their simulations. The purpose was to recreate experimental observations of rolling velocity changes with shear rate. The study sought to identify parameter ranges that produce the threshold effect. The motivation was to bridge the gap between molecular bond behavior and macroscopic cell dynamics. This approach allows for a deeper understanding of how bond mechanics influence rolling behavior.

The researchers used adhesive dynamics simulations to model cell rolling behavior. They implemented a catch-slip dissociation model for selectin bonds. A shear-controlled association rate was also included in the model. The simulations focused on L-selectin, which is known to mediate rolling. The model tracked rolling velocity as a function of shear rate. The simulations were run under varying shear conditions to test the threshold effect. The model included parameters for bond lifetime and force dependence. The researchers analyzed the output to determine how catch-slip behavior affects rolling velocity.

The simulations showed that rolling velocity has a minimum near 100 s⁻¹. This matches experimental observations of the shear threshold effect. Cells rolled at the threshold shear rate but detached when the rate dropped below it. The catch-slip behavior of bonds was sufficient to produce the threshold effect. The model predicted that L-selectin is most affected by this behavior. The simulations revealed a clear relationship between bond mechanics and rolling dynamics. The results suggest that catch bonds are necessary for rolling at low shear. Slip bonds dominate at high shear, leading to detachment. These findings support the hypothesis that catch-slip bonds are responsible for the threshold effect.

The authors concluded that catch-slip behavior in selectin bonds can explain the shear threshold effect. Their simulations successfully recreated the threshold seen in experimental data. The model showed that L-selectin is most sensitive to this effect. Rolling velocity is minimized at a shear rate near 100 s⁻¹. The simulations also showed that cells detach when shear drops below the threshold. The results suggest that catch bonds are crucial for rolling at low force. Slip bonds dominate at high force, leading to detachment. The authors propose that this mechanism is central to leukocyte rolling behavior.