Lessons learned from clustering of fluorinated glycolipids on selectin ligand function in cell rolling

Biochemistry
Gabriele SchumacherGerd Bendas

Abstract

Selectin-induced leukocyte rolling along the endothelium is an essential step in the cellular immune response. Since clustering of binding epitopes is thought to be crucial for selectin-ligand interaction, we focused on requirements of ligand clusters in a flow chamber study. Neoglycolipids bearing the binding epitope sialyl Lewis X (sLeX) were used as artificial ligands in model membranes. sLeX ligands or matrix lipids or both were applied with partially fluorinated alkyl chains to increase the ligand cluster separation tendency. Cluster size, their inner structure, and separation distance were evaluated with high resolution by scanning force microscopy (SFM) and correlated with binding or rolling of E-selectin-expressing cells. Fluorination of only one component, sLeX ligand or matrix lipid, leads to a very high separation tendency and impeded cell rolling, although firm cell adhesion could be observed down to 0.005 mol % ligand concentration. As a sign of total immiscibility, cluster size increased with ligand concentration, and resulting excessive ligand densities within the clusters prevent cell rolling. Fluorination of both sLeX ligands and matrix created small clusters which could serve as rolling patches. Our results co...Continue Reading

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Citations

Nov 1, 2011·Annals of Biomedical Engineering·Ruben T AlmarazKevin J Yarema
Jul 3, 2007·Journal of the American Chemical Society·Nicholas C YoderKrishna Kumar
Oct 10, 2006·Carbohydrate Research·Holger Herzner, Horst Kunz
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Aug 3, 2021·Chemical Reviews·Lu SuGuosong Chen
Nov 10, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Patrick ScheibeRudolf Zentel

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