Martini 3 coarse-grained model for chitosan with tunable acetylation

Chitosan, a polysaccharide produced via deacetylation of chitin, is widely used in biomedicine, food packaging, and environmental remediation due to its biocompatibility, antimicrobial properties, and tunable solubility. The deacetylation process is generally incomplete and produces random distributions of acetylated and deacetylated units with significant variability in chain composition, which makes it difficult to understand the relation between polymer structure and properties. In principle, molecular simulations can aid in such task, and illustrate how chain composition and solution conditions influence the solubility, size, flexibility, and aggregation behavior of the polymer. However, atomistic simulations are computationally costly, and therefore generally limited to systems containing few short chains, while real materials often contain hundreds or thousands of repeating units. To extend the scope of simulations and further explore the structural and functional properties of chitosan, we developed a coarse-grained model compatible with the Martini 3 force field. This model 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 chains in solution, as well as their interactions with lipid monolayers and, in particular, their distinct affinities for zwitterionic and anionic monolayers. The latter, upon interaction with chitosan, show an increased tensile strength. Overall, the model provides a robust tool for simulating chitosan in complex biological environments, as well as for designing chitosan-based drug and vaccine delivery systems.