Molecular basis of the dynamic strength of the sialyl lewis x-selectin interaction

Xiaohui Zhang, Daniela F. Bogorin, Vincent T. Moy

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The selectins are Ca2+-dependent cell adhesion molecules that facilitate the initial attachment of leukocytes to the vascular endothelium by binding to a carbohydrate moiety as exemplified by the tetrasaccharide, sialyl Lewis X (sLeX). An important property of the selectin-sLeX interaction is its ability to withstand the hydrodynamic force of the blood flow. Herein, we used single-molecule dynamic force spectroscopy (DFS) to identify the molecular determinants within sLeX that give rise to the dynamic properties of the selectin/sLeX interaction. Our atomic force microscopy (AFM) measurements revealed that the unbinding of the selectin/sLeX complexes involves overcoming at least two activation barriers. The inner barrier, which determines the dynamic response of the complex at high forces, is governed by the interaction between the Fuc residue of sLeX and a Ca2+ ion chelated to the lectin domain of the selectin molecule, whereas the outer activation barrier can be attributed to interactions involving the sialic acid residue of sLeX. Due to their steep inner activation barriers, the selectin-sLeX complexes are less sensitive to high pulling forces. Hence, besides its contribution to the bond energy, the Ca2+ ion also grants the selectin - sLeX complexes a tensile strength that is crucial for the selectin-mediated rolling of leukocytes.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalChemPhysChem
Volume5
Issue number2
DOIs
StatePublished - Feb 20 2004

Keywords

  • Cell adhesion
  • Energy landscapes
  • Scanning probe microscopy
  • Selectins
  • Sialyl Lewis X
  • Single-molecule studies

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics

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