Probing Single Icam-1/Lfa-1 Interaction under External Force.

Xiaohui Zhang,Ewa Wojcikiewicz,Vincent T Moy

doi:10.1100/tsw.2002.21

Abstract

RESULTS. The LFA-1/ICAM-1 bond was stretched by the cantilever until it finally ruptured, resulting in a sharp transition in the force-displacement curve. The measured unbinding force of the complex was derived from the magnitude of this transition. The unbinding of the LFA1/ICAM-1 complex by the application of external forces was examined in the context of the Bell model[4]. In this model, an applied force distorts the energy landscape of the LFA-1/ICAM-1 complex resulting in a lowering of the activation barrier(s). The AFM force measurements revealed two activation barriers in the dissociation of the LFA-1/ICAM-1 complex. The outer energy barrier was obtained at the slow loading regime of 10 to 10,000 pN/s. The for the dissociation of the low affinity LFA-1/ICAM-1 complex in this loading regime was 2 s , whereas the -1

Highlights

The interaction of lymphocyte function associated antigen-1 (LFA-1) with its ligand, intercellular adhesion molecule-1 (ICAM-1), mediates firm adhesion between leukocytes and vascular endothelial cells
The LFA-1/ICAM-1 bond was stretched by the cantilever until it ruptured, resulting in a sharp transition in the force-displacement curve
An applied force distorts the energy landscape of the LFA-1/ICAM-1 complex resulting in a lowering of the activation barrier(s)

Summary

Introduction

The interaction of lymphocyte function associated antigen-1 (LFA-1) with its ligand, intercellular adhesion molecule-1 (ICAM-1), mediates firm adhesion between leukocytes and vascular endothelial cells. AFM force measurements were carried out at 25°C using a home-built AFM[2] in RPMI 1640 medium. 3A9 cells (a murine T-cell hybridoma) were attached to the AFM cantilever by Con A-mediated linkages.

Results

Conclusion