title: Selectin catch-slip kinetics encode shear threshold adhesive behavior of rolling leukocytes.
abstract: The selectin family of leukocyte adhesion receptors is principally recognized for mediating transient rolling interactions during the inflammatory response. Recent studies using ultrasensitive force probes to characterize the force-lifetime relationship between P- and L-selectin and their endogenous ligands have underscored the ability of increasing levels of force to initially extend the lifetime of these complexes before disrupting bond integrity. This so-called "catch-slip" transition has provided an appealing explanation for shear threshold phenomena in which increasing levels of shear stress stabilize leukocyte rolling under flow. We recently incorporated catch-slip kinetics into a mechanical model for cell adhesion and corroborated this hypothesis for neutrophils adhering via L-selectin. Here, using adhesive dynamics simulations, we demonstrate that biomembrane force probe measurements of various P- and L-selectin catch bonds faithfully predict differences in cell adhesion patterns that have been described extensively in vitro. Using phenomenological parameters to characterize the dominant features of molecular force spectra, we construct a generalized phase map that reveals that robust shear-threshold behavior is possible only when an applied force very efficiently stabilizes the bound receptor complex. This criteria explains why only a subset of selectin catch bonds exhibit a shear threshold and leads to a quantitative relationship that may be used to predict the magnitude of the shear threshold for families of catch-slip bonds directly from their force spectra. Collectively, our results extend the conceptual framework of adhesive dynamics as a means to translate complex single-molecule biophysics to macroscopic cell behavior.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Beste
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000378:metabolism*; D036904:Leukocyte Rolling / Q000502:physiology*; D008954:Models, Biological; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D019041:L-Selectin