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-ECM adhesions, 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. Results demonstrated that HHA dominated the binding phase but LHA was in favor of the shear resistance phase, respectively, under shear stress range ≤ 1.0 dyne/cm2. This difference was attributed to the high binding strength of CD44-HHA interaction, as well as the optimal distribution matching between both CD44 and HA sides. Activation of the intercellular 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, and induce the increase of both CD44 and CD18 expression. This study offers the basis for further quantification of the features of CD44-HA interactions and their biological functions.