State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao, Shandong 266580, PR China.
Department of Common Courses, Weifang Medical University, Weifang, Shandong 261042, PR China.
Carbohydr Polym. 2018 Oct 1;197:326-336. doi: 10.1016/j.carbpol.2018.06.015. Epub 2018 Jun 5.
Hyaluronan (HA) possesses manifold mechanical and signaling properties in the body. Most of these activities are largely regulated by its molecular weight, which often triggers opposing functions. However the molecular basis for such function distinction between HA size categories remains unclear. Using a combination of biophysical techniques, we measured the physical forces between HA ligand and its specific receptor CD44 in both normal and lateral directions, at different HA molecular weights and bound states. It was found that the impact of HA multivalency is more than just the sum of separate monovalent bindings. The HA-CD44 specific interaction enhances with HA molecular weight and the maximum binding occurs at ∼1000 kD, possibly due to the balance between multivalent HA zipping effect and conformational entropy. High friction patches, probably from CD44 protein clustering, was observed in friction force microscopy (FFM) upon HA shearing, which is also dependent on HA molecular weight. These results could help to understand the biophysical mechanism of HA in regulating CD44-induced physiological activities and thus facilitate the new design of HA-based material in fine tuning the receptor responses.
透明质酸（HA）在体内具有多种机械和信号特性。这些活动中的大多数主要受其分子量的调节，分子量常常引发相反的功能。然而，HA 大小类别之间功能区分的分子基础仍不清楚。我们使用一系列生物物理技术，在不同的 HA 分子量和结合状态下，在正常和横向方向上测量了 HA 配体与其特定受体 CD44 之间的物理力。结果发现，HA 多价性的影响不仅仅是单独单价结合的总和。HA-CD44 的特异性相互作用随 HA 分子量的增加而增强，最大结合发生在约 1000kD 左右，这可能是由于多价 HA 拉链效应和构象熵之间的平衡。在 HA 剪切时，在摩擦力显微镜（FFM）中观察到高摩擦斑块，可能来自 CD44 蛋白聚集，这也依赖于 HA 分子量。这些结果有助于理解 HA 调节 CD44 诱导的生理活动的生物物理机制，从而有助于设计基于 HA 的新型材料，以精细调节受体反应。
