Martini 3 Coarse-Grained Model for Chitosan with Tunable Acetylation

Chitosan, a polysaccharide produced via partial deacetylation of chitin, is widely used in biomedicine, food packaging, and environmental remediation due to its biocompatibility, antimicrobial properties, and tunable solubility. Its incomplete deacetylation produces chains with significant variability in composition, making it difficult to understand the relation between polymer structure and properties. Molecular simulations can address this issue, but atomistic models are computationally demanding. To overcome this limitation, we developed a coarse-grained model compatible with the Martini 3 force field that accurately captures variations in the degree of acetylation and protonation states, enabling simulations of fully deacetylated chitosan, chitin, and intermediate forms. The model reproduces key structural properties of chitosan in solution, its pH-dependent self-assembly, and interactions with proteins and lipid monolayers, distinguishing affinities for zwitterionic and anionic lipids. Overall, the model provides a robust tool for simulating chitosan in complex environments and for designing chitosan-based drug and vaccine delivery systems.