Uncommon Structures of Oppositely Charged Hyaluronan/Surfactant Assemblies under Physiological Conditions

Self-assembled aggregates formed by semidilute polyanion hyaluronan (hyaluronic acid, HA) and an oppositely charged surfactant tetradecyltrimethylammonium bromide (TTAB) in an aqueous phosphate-buffered saline (PBS) solution have been studied via light scattering (LS), small-angle neutron scattering (SANS), and cryogenic transmission electron microscopy (cryo-TEM). The addition of 0–20 mM TTAB to a 27.7 mM (monomer, 1 wt %) HA solution (597 kDa) in PBS buffer leads to soluble complexes until phase separation occurs near charge equilibrium (>20 mM TTAB). While the viscosity remains rather constant, already small amounts of added TTAB lead to the formation of large globular superstructures, which are built in a hierarchical fashion from a locally threadlike structural arrangement of TTA micelles along the stiff HA chains, within the little changed HA network. These globular domains have radii of 60–100 nm and contain 500–700 TTA micelles, which means that they are very “fluffy” and composed of about 99% water. They do not grow in size or number upon further TTAB addition, but, instead, the additional TTA micelles form further threadlike complexes outside of the big globular domains. Such a type of polyelectrolyte–surfactant complexes (PESCs) has not been described before and has to be attributed to the particular properties of HA, which are high stiffness and relatively weak interactions with oppositely charged micelles due to having the charged carboxylic group close to the polysaccharide backbone. These findings demonstrate that the HA network structure in solution basically remains unaffected by complexation with an oppositely charged surfactant, explaining the unchanged rheological behavior and the formation of a unique PESC local “coacervate” structure within the HA hydrogel network.