The ubiquitous presence of hyaluronic acid (HA) in the extracellular matrix (ECM) of both healthy and diseased tissues underscores its importance in human physiology. Previous studies suggest that HA can be used as a probe to qualitatively monitor cell surface levels of CD44 and other important HA receptors; however, these studies use mixtures of HA at various molecular weights. Using fluorescently labeled HA, we evaluated the apparent differences of low (25 kilodalton) and high (700 kilodalton) molecular weight HA interacting with breast cancer cell lines of varying levels of CD44. Our results confirm that CD44 expression and the apparent level of HA interaction correlates with molecular weight. Importantly, we show that HA only binds a small fraction of the major CD44 isoform, CD44S, on cell surfaces and that CD44S interactions account for <50% of the total HA bound to cell surfaces. Although increased fluorescence level correlates with higher molecular weight of HA, this appears to be an artifact of chain length and not a result of multivalent binding between HA and CD44S. Accordingly, we verify that HA binding characteristics of cell surfaces is similar to previous artificial membrane models which proposed that HA anchors to CD44S and forms a non-binding corona of HA that extends beyond the surface.

中文翻译：

---

透明质酸与CD44S的结合是不分分子量的。

透明质酸（HA）在健康和患病组织的细胞外基质（ECM）中普遍存在，突显了其在人体生理学中的重要性。先前的研究表明，HA可以用作定性监测CD44和其他重要HA受体的细胞表面水平的探针。但是，这些研究使用了各种分子量的HA混合物。使用荧光标记的HA，我们评估了低分子量（25道尔顿）和高分子量（700道尔顿）HA与不同水平CD44的乳腺癌细胞相互作用的表观差异。我们的结果证实CD44表达和HA相互作用的表观水平与分子量相关。重要的是，我们显示HA仅结合细胞表面上一小部分主要的CD44亚型CD44S，并且CD44S相互作用占< 总HA的50％结合在细胞表面。尽管增加的荧光水平与HA的较高分子量有关，但这似乎是链长的假象，而不是HA与CD44S之间多价结合的结果。因此，我们验证了细胞表面的HA结合特性与先前的人工膜模型相似，后者提出HA锚定至CD44S并形成延伸至表面之外的HA非结合性电晕。