Analysis of the formation mechanism of polyion complexes of polysaccharides by molecular dynamics simulation with oligosaccharides

Polysaccharides have been extensively studied as biomaterials in various fields for their biocompatibility, biodegradability, and biological functions. To obtain water-insoluble materials from polysaccharides, polyion complexes (PICs) formed between cationic and anionic polysaccharides have been widely used in drug delivery systems and tissue engineering. Understanding the atomic interaction mechanism of oppositely charged polysaccharides is important in the design and application of PIC-based materials. In this work, the interaction between single-stranded chitosan and four kinds of anionic oligosaccharides was systematically investigated to elucidate the effects of the functional groups of chitosan and chemical species of anionic oligosaccharides on complex formation using molecular dynamics (MD) simulation with atomic detail. We verified that chitosan and anionic oligosaccharides form complexes, regardless of the functional groups of chitosan. For ‒NH3+ chitosan, due to the strong electrostatic interaction, a higher number of hydrogen bonds between ‒NH3+ in chitosan and anionic charged groups of anionic oligosaccharides were formed. Our results also suggested that ‒NH2 and ‒NHAc chitosan could form complexes with anionic oligosaccharides due to hydrogen bonds. These findings might be important for the design and stabilization of PICs based on polysaccharides.