Binding of different hyaluronan to CD44 mediates distinct cell adhesion dynamics under shear flow
Binding of different hyaluronan to CD44 mediates distinct cell adhesion dynamics under shear flow
复制标题
DOI：
10.1111/febs.16882
复制
发表时间：
2023-06-16
期刊：
影响因子：
5.4
通讯作者：
Lu，Shouqin
中科院分区：
文献类型：
--
作者：
Li，Linda;Ding，Qihan;Lu，Shouqin
作为已知的介导细胞-细胞或细胞-细胞外基质粘附的受体-配体对，分化簇44（CD 44）-透明质酸（HA）相互作用不仅由HA的分子量（MW）多样性决定，而且还受外部物理或机械因素调节。然而，HA MW和剪切流的耦合效应仍然不清楚。在这里，我们比较了高分子量HA（HHA）和低分子量HA（LHA）之间的差异结合CD 44在不同的剪切应力。结果表明，在剪切应力≤ 1.0 dyne·cm−2范围内，HHA在粘结相占主导地位，而LHA在抗剪切相占主导地位。这种差异归因于CD 44-HHA相互作用的高结合强度，以及CD 44和HA侧之间的最佳分布匹配。细胞内信号通路的激活对HA MW和剪切流都敏感。我们的研究结果还表明，只有在0.2 dyne·cm− 2的剪切应力下，CD 44-HHA相互作用才能显著增强CD 44的聚集，并诱导CD 44和CD 18表达的增加。本研究为进一步定量CD 44-HA相互作用的特征及其生物学功能提供了基础。
As a known receptor–ligand pair for mediating cell–cell or cell–extracellular matrix adhesions, cluster of differentiation 44 (CD44)‐hyaluronan (HA) interactions are not only determined by molecular weight (MW) diversity of HA, but also are regulated by external physical or mechanical factors. However, the coupling effects of HA MW and shear flow are still unclear. Here, we compared the differences between high molecular weight HA (HHA) and low molecular weight HA (LHA) binding to CD44 under varied shear stresses. The results demonstrated that HHA dominated the binding phase but LHA was in favour of the shear resistance phase, respectively, under shear stress range ≤ 1.0 dyne·cm−2. This difference was attributed to the high binding strength of the CD44–HHA interaction, as well as the optimal distribution matching between both CD44 and HA sides. Activation of the intracellular signal pathway was sensitive to both HA MW and shear flow. Our findings also indicate that only CD44–HHA interaction under shear stress of 0.2 dyne·cm−2could significantly enhance the clustering of CD44, as well as induce the increase in both CD44 and CD18 expression. The present study offers the basis for further quantification of the features of CD44–HA interactions and their biological functions.