Distribution of Sialic Acids on Mucins and Gels: A Defense Mechanism
Distribution of Sialic Acids on Mucins and Gels: A Defense Mechanism
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DOI：
10.1016/j.bpj.2011.08.058
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发表时间：
2012-01-04
影响因子：
3.4
通讯作者：
Berry, M.
中科院分区：
文献类型：
--
作者：
Baos, S. C.;Phillips, D. B.;Berry, M.
暴露于外部环境的湿润粘膜上皮界面由糖表位主导，其中一些（例如，唾液酸）参与宿主防御。在这项研究中，我们确定了两个唾液酸的丰度和分布，以评估其可用性的差异，以外源性探针分离粘蛋白和粘液凝胶。我们使用原子力显微镜，以获得力地图的人眼前粘液和纯化的眼粘蛋白探针和定位之间的相互作用的尖端栓系凝集素怀槐和接骨木及其各自的受体，α-2，3和α-2，6 N-乙酰神经氨酸（唾液酸）。断裂力分布不受相邻的含糖分子的影响。两个凝集素-糖键的能量轮廓拟合到一个双势垒模型，表明解离前的构象变化。与来自纯化粘蛋白分子的数据相反，眼前凝胶呈现出大量α-2，6唾液酸的大簇（19，000 +/- 4000 nm（2）），但很少有α-2，3表位的小簇（2000 +/- 500 nm（2））。这表明富含α-2，3唾液酸的粘蛋白仅部分暴露在粘液凝胶的表面。识别α-2，3唾液酸的微生物将仅遇到分离的配体，并且其他微生物的粘附将通过邻近α-2，6唾液酸的大岛来增强。我们揭示了粘膜表面异质性的另一个水平，特别是在保护下层上皮细胞免受病毒和细菌侵害的促粘附和抗粘附唾液酸的分布中。
Moist mucosal epithelial interfaces that are exposed to external environments are dominated by sugar epitopes, some of which (e.g., sialic acids) are involved in host defense. In this study, we determined the abundance and distribution of two sialic acids to assess differences in their availability to an exogenous probe in isolated mucins and mucous gels. We used atomic force microscopy to obtain force maps of human preocular mucous and purified ocular mucins by probing and locating the interactions between tip-tethered lectins Maackia amurensis and Sambucus nigra and their respective receptors, alpha-2,3 and alpha-2,6 N-acetylneuraminic (sialic) acids. The rupture force distributions were not affected by neighboring sugar-bearing molecules. Energy contours for both lectin-sugar bonds were fitted to a two-barrier model, suggesting a conformational change before dissociation. In contrast to data from purified mucin molecules, the preocular gels presented numerous large clusters (19,000 +/- 4000 nm(2)) of alpha-2,6 sialic acids, but very few small clusters (2000 +/- 500 nm(2)) of alpha-2,3 epitopes. This indicates that mucins, which are rich in alpha-2,3 sialic acids, are only partially exposed at the surface of the mucous gel. Microorganisms that recognize alpha-2,3 sialic acids will encounter only isolated ligands, and the adhesion of other microorganisms will be enhanced by large islands of neighboring alpha-2,6 sialic acids. We have unveiled an additional level of mucosal surface heterogeneity, specifically in the distribution of pro- and antiadhesive sialic acids that protect underlying epithelia from viruses and bacteria.