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. 2004 Sep 13;166(6):913-23.
doi: 10.1083/jcb.200403144.

Catch bonds govern adhesion through L-selectin at threshold shear

Tadayuki Yago  1 , Jianhua Wu, C Diana Wey, Arkadiusz G Klopocki, Cheng Zhu, Rodger P McEver
Affiliations

Catch bonds govern adhesion through L-selectin at threshold shear

Tadayuki Yago et al. J Cell Biol. .

Erratum in

  • J Cell Biol. 2005 Mar 14;168(6):975

Abstract

Flow-enhanced cell adhesion is an unexplained phenomenon that might result from a transport-dependent increase in on-rates or a force-dependent decrease in off-rates of adhesive bonds. L-selectin requires a threshold shear to support leukocyte rolling on P-selectin glycoprotein ligand-1 (PSGL-1) and other vascular ligands. Low forces decrease L-selectin-PSGL-1 off-rates (catch bonds), whereas higher forces increase off-rates (slip bonds). We determined that a force-dependent decrease in off-rates dictated flow-enhanced rolling of L-selectin-bearing microspheres or neutrophils on PSGL-1. Catch bonds enabled increasing force to convert short-lived tethers into longer-lived tethers, which decreased rolling velocities and increased the regularity of rolling steps as shear rose from the threshold to an optimal value. As shear increased above the optimum, transitions to slip bonds shortened tether lifetimes, which increased rolling velocities and decreased rolling regularity. Thus, force-dependent alterations of bond lifetimes govern L-selectin-dependent cell adhesion below and above the shear optimum. These findings establish the first biological function for catch bonds as a mechanism for flow-enhanced cell adhesion.

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Figures

Figure 1.
Figure 1.
Parameters of rolling adhesion under flow. (A) The rolling motions of a microsphere or neutrophil of radius r are governed by the balance of the resultant force (F s) and torque (T s) exerted by the flowing fluid, the tether force (F t) applied through L-selectin–PSGL-1 bonds, and the contact force (F c). The conversion of wall shear stress to F t using the indicated variables is described in Materials and methods. Elevating the viscosity by addition of 6% Ficoll increases shear stress by 2.6-fold and therefore increases F t on a sphere of constant size, as illustrated by the comparative lengths of the thin and thick vectors for F t on the small sphere. At the same shear stress, F t is ninefold greater for a sphere of 3-μm radius than for a sphere of 1-μm radius, as illustrated by the comparative lengths of the thin vectors for F t on the large and small spheres. (B) A rolling sphere stops when the adhesive bond sustains the full load required to balance the maximum F t and T s. After the bond dissociates, the sphere accelerates as it pivots on a newly formed bond upstream and then decelerates as force develops in the bond. The sphere stops again if the new bond has sufficient strength to withstand the full load and lives long enough to survive loading, or it accelerates if the bond dissociates prematurely.
Figure 2.
Figure 2.
Tether force governs rolling velocity below and above the flow optimum. Mean velocities of L-selectin–bearing microspheres of 3- or 1-μm radii (A–C) or of unfixed or fixed neutrophils (D–F) rolling on sPSGL-1 (140 sites/μm2) in the absence or presence of 6% Ficoll were plotted against wall shear rate, wall shear stress, and tether force. A logarithmic scale was used to plot the broad range of wall shear rates and wall shear stresses, whereas a linear scale was used to plot tether forces. The data represent the mean ± SD of five experiments.
Figure 3.
Figure 3.
Tether force governs off-rates of transient tethers below and above the flow optimum. Off-rates (k off) derived from lifetimes of transient tethers of L-selectin–bearing microspheres of 3- or 1-μm radii (A–C) or of unfixed or fixed neutrophils (D–F) to low density sPSGL-1 (<10 sites/μm2) in the absence or presence of 6% Ficoll were plotted against wall shear rate, wall shear stress, and tether force. A logarithmic scale was used to plot the broad range of wall shear rates and wall shear stresses, whereas a linear scale was used to plot tether forces. The data represent the mean ± SD of five experiments.
Figure 4.
Figure 4.
Changing features of instantaneous rolling velocity below and above the flow optimum. Shown are instantaneous velocities of representative L-selectin–bearing microspheres of 3-μm radii rolling on sPSGL-1 (140 sites/μm2) in the absence of Ficoll at wall shear rates (s−1) and corresponding tether forces (pN) below and above the optimum. The data were recorded at 250 fps. The top left panel shows the comparative instantaneous velocities of microspheres freely flowing over an HSA-coated surface at wall shear rates up to 50 s−1 (potential tether forces up to 60 pN), where velocity fluctuations could be accurately measured.
Figure 5.
Figure 5.
Quantification of rolling parameters below and above the flow optimum. Stop frequencies (A), mean stop times (B), fractional stop times (C), go frequencies (D), fractions of steps with stops (E), and fractional go times (F) for 3-μm microspheres rolling on PSGL-1 or freely flowing over HSA in the absence of Ficoll were plotted against tether force (linear scale). The data were recorded at 250 fps.
Figure 6.
Figure 6.
Tether force governs rolling stop frequencies below and above the flow optimum. Nearly a thousand stop events measured at 250 fps for each flow rate were collected from 10–15 L-selectin–bearing microspheres of 1- or 3-μm radii (A–C) or unfixed and fixed neutrophils (D–F), each continuously rolling for 1 s on sPSGL-1 (140 sites/μm2) in the absence or presence of 6% Ficoll. The stop frequencies were plotted against wall shear rate (logarithmic scale), wall shear stress (logarithmic scale), and tether force (linear scale).
Figure 7.
Figure 7.
Tether force governs rolling stop times below and above the flow optimum. The mean stop times of the rolling microspheres and neutrophils described in Fig. 6 were plotted against wall shear rate (logarithmic scale), wall shear stress (logarithmic scale), and tether force (linear scale).
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References

    1. Alon, R., D.A. Hammer, and T.A. Springer. 1995. Lifetime of the P-selectin: carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature. 374:539–542. - PubMed
    1. Alon, R., S.Q. Chen, K.D. Puri, E.B. Finger, and T.A. Springer. 1997. The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling. J. Cell Biol. 138:1169–1180. - PMC - PubMed
    1. Bell, G.I. 1978. Models for the specific adhesion of cells to cells. Science. 200:618–627. - PubMed
    1. Bruehl, R.E., T.A. Springer, and D.F. Bainton. 1996. Quantitation of L-selectin distribution on human leukocyte microvilli by immunogold labeling and electron microscopy. J. Histochem. Cytochem. 44:835–844. - PubMed
    1. Chang, K.-C., and D.A. Hammer. 1999. The forward rate of binding of surface-tethered reactants: effect of relative motion between two surfaces. Biophys. J. 76:1280–1292. - PMC - PubMed

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