Flow-enhanced adhesion regulated by a selectin interdomain hinge

J Cell Biol. 2006 Sep 25;174(7):1107-17. doi: 10.1083/jcb.200606056.


L-selectin requires a threshold shear to enable leukocytes to tether to and roll on vascular surfaces. Transport mechanisms govern flow-enhanced tethering, whereas force governs flow-enhanced rolling by prolonging the lifetimes of L-selectin-ligand complexes (catch bonds). Using selectin crystal structures, molecular dynamics simulations, site-directed mutagenesis, single-molecule force and kinetics experiments, Monte Carlo modeling, and flow chamber adhesion studies, we show that eliminating a hydrogen bond to increase the flexibility of an interdomain hinge in L-selectin reduced the shear threshold for adhesion via two mechanisms. One affects the on-rate by increasing tethering through greater rotational diffusion. The other affects the off-rate by strengthening rolling through augmented catch bonds with longer lifetimes at smaller forces. By forcing open the hinge angle, ligand may slide across its interface with L-selectin to promote rebinding, thereby providing a mechanism for catch bonds. Thus, allosteric changes remote from the ligand-binding interface regulate both bond formation and dissociation.

Publication types

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

MeSH terms

  • Cell Adhesion
  • Humans
  • L-Selectin / metabolism*
  • Leukocyte Rolling / physiology*
  • Leukocytes / physiology*
  • Ligands
  • Models, Biological
  • Molecular Conformation
  • Monte Carlo Method
  • Shear Strength


  • Ligands
  • L-Selectin