Understanding mucus modulation behavior of chitosan oligomers and dextran sulfate combining light scattering and calorimetric observations

This study reports the fundamental understanding of mucus-modulatory strategies combining charged bio-polymers with distinct molecular weights and surface charges. Here, key biophysical evidence supports that low-molecular-weight (Mw) polycation chitosan oligosaccharides (COSs) and high-Mw polyanion dextran sulfate (DS) exhibit distinct thermodynamic signatures upon interaction with mucin (MUC), the main protein of mucus. While the COS -> MUC microcalorimetric titrations released-14 kcal/mol and-60 kcal/mol, the DS -> MUC titrations released-1200 and-1450 kcal/mol at pH of 4.5 and 6.8, respectively. The MPT-2 titrations of COS -> MUC and DS -> MUC indicated a greater zeta potential variation at pH = 4.5 (relative variation = 815 % and 351 %, respectively) than at pH = 6.8 (relative variation = 282 % and 136 %, respectively). Further, the resultant binary (COS-MUC) and ternary (COS-DS-MUC) complexes showed opposite behavior (aggregation and charge inversion events) according to the pH environment. Most importantly, the results indicate that electrostatics could not be the driving force that governs COS-MUC interactions. To account for this finding, we proposed a two-level abstraction model. Macro features emerge collectively from individual interactions occurring at the molecular level. Therefore, to understand the outcomes of mucus modulatory strategy based on charged bio-polymers it is necessary to integrate both visions into the same picture.