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Molecular Basis for the Dynamic Strength of the Integrin a^sub 4^B^sub 1^/VCAM-1 Interaction

ABSTRACT

Intercellular adhesion mediated by integrin ?^sub 4^?^sub 1^ and vascular cell adhesion molecule-1 (VCAM-1) plays a crucial role in both the rolling and firm attachment of leukocytes onto the vascular endothelium. Essential to the ?^sub 4^?^sub 1^/VCAM-1 interaction is its mechanical strength that allows the complex to resist the large shear forces imposed by the bloodstream. Herein we employed single-molecule dynamic force spectroscopy to investigate the dynamic strength of the ?^sub 4^?^sub 1^/VCAM-1 complex. Our force measurements revealed that the dissociation of the ?^sub 4^?^sub 1^/VCAM-1 complex involves overcoming at least two activation potential barriers: a steep inner ...

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