Single-molecule binding of CD44 to fibrin versus P-selectin predicts their distinct shear-dependent interactions in cancer
Year: 2011
Type: article
Abstract: P-selectin and fibrin(ogen) have pivotal roles in the hematogenous dissemination of tumor cells. CD44 variant isoforms, CD44v, have been identified as the major functional P-selectin ligands and fibrin receptors on metastatic colon carcinoma cells. The molecular recognition of CD44v by fibrin mediates firm adhesion at low shear, whereas CD44v-P-selectin binding supports transient rolling interactions at elevated shear stresses and low site densities of P-selectin. We used single-molecule force spectroscopy to provide a molecular interpretation for these two distinct adhesion events. The CD44v-P-selectin bond has a longer unstressed equilibrium lifetime, a lower reactive compliance and a higher tensile strength relative to the CD44v-fibrin bond. These intrinsic differences confer the ability to the CD44v-P-selectin pair to mediate binding at higher shear stresses. Increasing the duration of receptor-ligand contact (2-200 milliseconds) did not affect the micromechanical properties of the CD44v-P-selectin bond, but it increased the tensile strength and the depth of the free energy barrier of the CD44v-fibrin bond and decreased its reactive compliance. This bond strengthening at longer interaction times might explain why CD44v binding to immobilized fibrin occurs at low shear. Single-molecule characterization of receptor-ligand binding can predict the shear-dependent adhesive interactions between cells and substrates observed both in vitro and in vivo.
Source: Journal of Cell Science
DOI: 10.1242/jcs.079814
Institution: Johns Hopkins University
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2105876866