Molecular Dynamics Simulations of The Interaction Between Chitosan and Bacterial Membranes

Objective Chitosan (CS) is a natural broad-spectrum antibacterial active substance. Previous studies revealed that the interaction between chitosan and bacterial cell membrane play a key role in its antibacterial activity. However, Due to the limited characterizing capability of current experimental techniques, the exact mechanism of the interaction between chitosan and bacterial cell membranes remains to be studied. This paper aims to study the molecular mechanism of the interaction between chitosan and bacterial cell membranes. Methods In this study, all-atom molecular dynamics simulations were used to explore the dynamic interaction between totally deacetylated chitosan in different degrees of polymerization (8-, 12-, and 16-saccharides) with the outer membrane (OM) of Gram-negative bacteria and the cytoplasmic membrane (CM) of Gram-positive bacteria. Results The amino groups, carbon 6 hydroxyl groups and carbon 3 hydroxyl groups of chitosan play the determinant role in the initial attachment to the polar headgroup regions of the OM and CM. Interestingly, the terminal glycosyl units of chitosan inserted into the OM with an averaged depth of 1 nm where the sugar formed stable hydrogen bonds with the carbonyl groups on the fatty acid tails of the OM lipid A molecules. In contrast, chitosan could not insert into the CM steadily. Further, we found that the binding of chitosan to both OM and CM reduced their area per lipid, displacing the Ca2+ and Na+ from the headgroup regions of the membranes and thereby attenuating the cation-mediated interactions between membrane lipids. Conclusion Our results demonstrated that the positively charged amino groups of chitosan are essential for the interaction with bacterial membranes, which reduced the interlipid interactions and lead to the structural disorganization of bacterial membranes. These information provides new insights into the antimicrobial mechanism of chitosan at the atomic level.