Cooperation between Lateral Ligand Mobility and Accessibility for Receptor Recognition in Selectin-Induced Cell Rolling
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- 作者：Udo Bakowsky ; Gabriele Schumacher ; Christian Gege ; Richard R. Schmidt ; Ulrich Rothe ; and Gerd Bendas
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：April 9, 2002
- 年：2002
- 卷：41
- 期：14
- 页码：4704 - 4712
- 全文大小：412K
- 年卷期：v.41,no.14(April 9, 2002)
- ISSN：1520-4995
文摘
Selectin-induced leukocyte rolling along the endothelial surface is an essential step in theimmune response. Several in vitro studies showed that this cell rolling is a highly regulated adhesionphenomenon, controlled by the kinetics and forces of selectin-ligand interactions. In the flow chamberstudy presented here, we focused on the requirements on the ligand structure in this context. A series ofneoglycolipids bearing the binding epitope Sialyl Lewis X was synthesized and used as artificial ligands.These lipids differed in their spacer structures between headgroup and membrane anchor, resulting in agradual variation in accessibility and mobility of the binding epitope when immobilized in modelmembranes. Consequently, analysis of cell rolling along such membranes allowed correlation of ligandstructures and functionality. All model membranes containing such ligands were further characterized byfilm balance measurements, epifluorescence, and atomic force microscopy. Generally, the glycolipidsexhibited a high tendency for lateral aggregation, but the resulting clusters were of different morphology.This was also reflected by strong differences in the rolling experiments. Our results confirm that, in additionto a sufficient headgroup accessibility, the cell rolling process is governed by two further interdependentfactors: (i) the headgroup flexibility caused by the intramolecular uncoupling between the headgroupand the hydrophobic moiety due to introduction of a spacer, and (ii) the stiffness of the molecules resultingfrom their supramolecular arrangement in clustered assemblies. Since both factors are influencedsimultaneously by the spacer modification, we present for the first time a clear correlation between structuralaspects of selectin ligands and their ability to mediate cell rolling. This might help to develop a betterunderstanding for the function of the natural selectin ligands.