Flow-enhanced adhesion regulated by a selectin interdomain hinge

• Type of Material: Article
• Authors: Jizhong Lou, Georgia Institute of Technology; Tadayuki Yago, Oklahoma Medical Research Foundation; Arkadiusz G. Klopocki, Oklahoma Medical Research Foundation; Padmaja Mehta, Oklahoma Medical Research Foundation; Wei Chen, Georgia Institute of Technology; Veronika Zarnitsyna, Emory University; Nicolai V. Bovin, Russian Academy of Sciences; Cheng Zhu, Emory University; Rodger P. McEver, Oklahoma Medical Research Foundation
• Language: English
• Date: 2006-09-25
• Publisher: ROCKEFELLER UNIV PRESS
• Publication Version: Final Published Version
• Copyright Statement: © The Rockefeller University Press.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.200606056
• Title of Journal or Parent Work: JOURNAL OF CELL BIOLOGY
• Volume: 174
• Issue: 7
• Start Page: 1107
• End Page: 1117
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health.
• Keywords: CATCH BONDS; Cell Biology; P-SELECTIN; FORCE; Life Sciences & Biomedicine; BINDING; SHEAR; Science & Technology; CELL-ADHESION; BACTERIAL ADHESION; MOLECULAR-DYNAMICS; GLYCOPROTEIN LIGAND-1; VON-WILLEBRAND-FACTOR
• Research Categories: Biology, Cell

Abstract

L-selectin requires a threshold shear to enable leukocytes to tether to and roll on vascular surfaces. Transport mechanisms govern flow-enhanced tethering, whereas force governs flow-enhanced rolling by prolonging the lifetimes of L-selectin-ligand complexes (catch bonds). Using selectin crystal structures, molecular dynamics simulations, site-directed mutagenesis, single-molecule force and kinetics experiments, Monte Carlo modeling, and flow chamber adhesion studies, we show that eliminating a hydrogen bond to increase the flexibility of an interdomain hinge in L-selectin reduced the shear threshold for adhesion via two mechanisms. One affects the on-rate by increasing tethering through greater rotational diffusion. The other affects the off-rate by strengthening rolling through augmented catch bonds with longer lifetimes at smaller forces. By forcing open the hinge angle, ligand may slide across its interface with L-selectin to promote rebinding, thereby providing a mechanism for catch bonds. Thus, allosteric changes remote from the ligand-binding interface regulate both bond formation and dissociation.