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Structure‐function of MAdCAM‐1 revealed by single‐molecule force spectroscopy
Author(s) -
Zhang Xiaohui,
Seog Joonil,
Springer Timothy A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb119-b
Subject(s) - addressin , force spectroscopy , mucin , chemistry , biophysics , cell adhesion molecule , cell adhesion , adhesion , molecule , immunoglobulin domain , microbiology and biotechnology , nanotechnology , biochemistry , materials science , biology , receptor , organic chemistry
Mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) is an endothelial adhesion molecule that mediates lymphocyte infiltration into mucosal lymphoid tissues. The extracellular portion of MAdCAM‐1 contains two N‐terminal immunoglobulin (Ig) domains and one heavily O‐glycosylated, more C‐proximal mucin‐like domain. Although the structure of MAdCAM‐1 is well‐characterized, it is not clear how these three domains facilitate the force‐resistant adhesion in shear flow. Here, we used single molecule atomic force microscopy (AFM) techniques to examine the mechanical properties of each domains of MAdCAM‐1. We find that the two Ig domains are mechanically stable and are able to resist pulling force of at least 120 pico‐Newton. Stretching of a single mucin‐like domain yielded a persistence length, a measure of nonlinear elasticity, comparable to the PEVK domain of giant muscle protein titin, suggesting that mucin‐like domain has a similar function as the PEVK for buffering external forces. Removal of O‐linked glycans from the mucin‐like domain decreased its persistence length and destabilized leukocyte rolling on immobilized MAdCAM‐1. Together, our data suggest that MAdCAM‐1 has a unique combination of two mechanically stable ligand‐binding domains and a more elastic mucin domain that is suitable for buffering the tensile force in shear flow. This work was supported by grants from the NIH and a fellowship from the AHA. Authors thank Dr. Julio Fernandez for providing AFM design and training.