Hyaluronan - a new player in adhesion and migration regulation

Single and collective cell migration are fundamental in development, maintenance and the progression of diseases across multicellular organisms. Although the factors regulating adhesion and migration have been extensively studied, hyaluronan - a high molecular weight and microns long polysaccharide forming the pericellular matrix around migrating cells, has been mostly neglected. It is well established that an intermediate cell-substrate adhesion strength, given by an intermediate extracellular matrix density, produces maximum speed; while deviations from that density reduce it. Our data suggest that hyaluronan at the cell-substrate interface regulates the adhesion strength by exerting repulsive forces counteracting focal adhesions. While overexpression of hyaluronan has been shown to promote cell migration and the opposite for low expression levels, our preliminary data suggest a more complex relation. We show that the level of expression and the spatial distribution of hyaluronan at the cell-substrate interface, together with the surface density of extracellular matrix proteins, regulate cell adhesion and migration.