Binding of different hyaluronan to CD44 mediates distinct cell adhesion dynamics under shear flow

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^-2 could 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.