Low force decelerates L-selectin dissociation from P-selectin glycoprotein ligand-1 and endoglycan.
Selectin-ligand interactions mediate the tethering and rolling of circulating leukocytes on vascular surfaces during inflammation and immune surveillance. To support rolling, these interactions are thought to have rapid off-rates that increase slowly as wall shear stress increases. However, the increase of off-rate with force, an intuitive characteristic named slip bonds, is at odds with a shear threshold requirement for selectin-mediated cell rolling. As shear drops below the threshold, fewer cells roll and those that do roll less stably and with higher velocity. We recently demonstrated a low force regime where the off-rate of P-selectin interacting with P-selectin glycoprotein ligand-1 (PSGL-1) decreased with increasing force. This counter-intuitive characteristic, named catch bonds, might partially explain the shear threshold phenomenon. Because L-selectin-mediated cell rolling exhibits a much more pronounced shear threshold, we used atomic force microscopy and flow chamber experiments to determine off-rates of L-selectin interacting with their physiological ligands and with an antibody. Catch bonds were observed at low forces for L-selectin-PSGL-1 interactions coinciding with the shear threshold range, whereas slip bonds were observed at higher forces. These catch-slip transitional bonds were also observed for L-selectin interacting with endoglycan, a newly identified PSGL-1-like ligand. By contrast, only slip bonds were observed for L-selectin-antibody interactions. These findings suggest that catch bonds contribute to the shear threshold for rolling and are a common characteristic of selectin-ligand interactions.
Sarangapani
Krishna K
KK
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Yago
Tadayuki
T
Klopocki
Arkadiusz G
AG
Lawrence
Michael B
MB
Fieger
Claudia B
CB
Rosen
Steven D
SD
McEver
Rodger P
RP
Zhu
Cheng
C
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D019041:L-Selectin / Q000737:chemistry* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D009077:Mucins / Q000737:chemistry* / Q000378:metabolism
D008562:Membrane Glycoproteins; D009077:Mucins; C084882:P-selectin ligand protein; C406902:endoglycan; D019041:L-Selectin