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Published 13 September 2004. doi:10.1083/jcb.200403144
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 6, 913-923
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Article

 Catch bonds govern adhesion through L-selectin at threshold shear

Tadayuki Yago1, Jianhua Wu3, C. Diana Wey4, Arkadiusz G. Klopocki1, Cheng Zhu4,5, and Rodger P. McEver1,2

1 Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
2 Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
3 School of Life Sciences, Zhongshan University, Guangzhou 510275, China
4 Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332
5 Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332

Address correspondence to Cheng Zhu, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0405. Tel.: (404) 894-3269. Fax: (404) 385-1397. email: cheng.zhu{at}me.gatech.edu; or Rodger P. McEver, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK 73104. Tel.: (405) 271-6480. Fax: (405) 271-3137. email: rodger-mcever{at}omrf.ouhsc.edu

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.

Key Words: leukocyte; PSGL-1; inflammation; lymphocyte homing; selectin

Abbreviations used in this paper: fps, frames per second; HSA, human serum albumin; PSGL-1, P-selectin glycoprotein ligand-1; sPSGL-1, soluble PSGL-1.


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