ABSTRACT
CD44 is a cell receptor glycoprotein overexpressed in circulating tumor cells (CTCs), with levels linked to an increase in metastatic capacity of several tumors. Hyaluronic acid (HA), the natural ligand of CD44, has primarily been investigated for tumor cell interaction in self-assembled polyelectrolyte multilayer films, with little attention given to the complementary polycation. In this study, we screened sixteen different polyelectrolyte multilayer assemblies of HA and chitosan (CHI) to identify key assembly parameters and surface properties that control and govern CTCs adhesion. Statistics analysis revealed a major role of CHI molecular weight in the adhesion, followed by its combinatorial response either with HA ionization degree or ionic strength. PM-IRRAS analysis demonstrated a correlation between the orientation of HA carboxyl groups on the film surface and CTCs adhesion, directly impacted by CHI molecular weight. Overall, although CTCs binding onto the surface of multilayer films is primarily driven by HA-CD44 interaction, both chitosan properties and film assembly conditions modulate this interaction. These findings illustrate an alternative to modifying the performance of biomaterials with minimal changes in the composition of multilayer films.