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Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow

Nature volume 374, pages 539–542 (1995)Cite this article

Abstract

SELECTINS tether to the blood vessel wall leukocytes that are flowing in the bloodstream and support subsequent labile rolling interactions as the leukocytes are subjected to hydrodynamic drag forces1,2. To support this rolling, selectins have been proposed to have rapid bond association and dissociation rate constants, and special mechanical properties linking tensile forces and bond dissociation3-6. We have visualized transient tethering and release of neutrophils in hydrodynamic flow on lipid bilayers containing densities of P-selectin below those required to support rolling. We report here that transient tethers had first-order kinetics and other characteristics suggesting a unimolecular interaction between P-selectin and its glycoprotein ligand (PSGL-1). The unstressed dissociation constant (off rate) was 1 s-1. Hydrodynamic shear stresses of up to 1.1 dyn cm-2, corresponding to a force on the bond of up to HOpN, increased the off rate only modestly, to 3.5 s-1. The data was adequately matched by a proposed equation7 relating off rate to the exponential of tensile force on the bond and the bond interaction distance, and gave a bond interaction distance of 0.5Å. This distance is compatible with hydrogen and metal coordination bonds between P-selectin and PSGL-1. Fast on and off rates, together with the high tensile strength of the selectin bond, appear necessary to support rolling at physiological shear stresses.

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Authors and Affiliations

  1. The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Ronen Alon & Timothy A. Springer

  2. School of Chemical Engineering, Cornell University, Ithaca, New York, 14853, USA

    Daniel A. Hammer

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  1. Ronen Alon
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Alon, R., Hammer, D. & Springer, T. Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374, 539–542 (1995). https://doi.org/10.1038/374539a0

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