Adhesive dynamics simulations of the mechanical shedding of L-selectin from the neutrophil surface

J Theor Biol. 2009 Sep 7;260(1):27-30. doi: 10.1016/j.jtbi.2009.05.014. Epub 2009 May 30.

Abstract

Here we accurately recreate the mechanical shedding of L-selectin and its effect on the rolling behavior of neutrophils in vitro using the adhesive dynamics simulation by incorporating the shear-dependent shedding of L-selectin. We have previously shown that constitutively expressed L-selectin is cleaved from the neutrophil surface during rolling on a sialyl Lewis x-coated planar surface at physiological shear rates without the addition of exogenous stimuli. Utilizing a Bell-like model to describe a shedding rate which presumably increases exponentially with force, we were able to reconstruct the characteristics of L-selectin-mediated neutrophil rolling observed in the experiments. First, the rolling velocity was found to increase during rolling due to the mechanical shedding of L-selectin. When most of the L-selectin concentrated on the tips of deformable microvilli was cleaved by force exerted on the L-selectin bonds, the cell detached from the reactive plane to join the free stream as observed in the experiments. In summary, we show through detailed computational modeling that the force-dependent shedding of L-selectin can explain the rolling behavior of neutrophils mediated by L-selectin in vitro.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Adhesion / physiology
  • Humans
  • L-Selectin / metabolism*
  • L-Selectin / physiology
  • Leukocyte Rolling / physiology
  • Mechanotransduction, Cellular / physiology
  • Models, Cardiovascular*
  • Neutrophils / metabolism*
  • Neutrophils / physiology
  • Shear Strength / physiology

Substances

  • L-Selectin