Interaction of chitosan derivatives with cell membrane models in a biologically relevant medium

[Display omitted] •Langmuir films of DPPC and DPPG are used as cell membrane models for mammal and bacterial cells.•Effects of chitosans on Langmuir films are probed using phosphate buffer (PBS) subphase.•SFG vibrational spectroscopy provides information about the chain conformation of lipids.•Results depend on the methodology: film formation in the presence of chitosan vs. its injection under a condensed film.•Interaction mechanism of chitosan with DPPC and DPPG lipids may explain why chitosan is antibacterial but not toxic to mammals. The interaction of chitosan, a natural biopolymer with various biomedical applications, with lipid Langmuir films has been widely investigated as a simple model for cell membranes. However, to ensure polymer solubility, up to now only acidic subphases with pH significantly below biological fluids have been used. To increase the biological significance of these investigations, here we evaluated the effects of two chitosan derivatives (low molecular weight − CH, and positively charged − CH-P40) on phospholipid films (either zwitterionic DPPC or anionic DPPG) using phosphate buffered saline solutions (PBS) as a subphase. Surface pressure − area (π−A) isotherms were used to evaluate the expansion and changes in film elasticity, while Sum-Frequency Generation (SFG) vibrational spectroscopy provided information about the chain conformation of lipids. It was found that chitosans caused a small expansion of the DPPC film by its insertion within the monolayer. In contrast, they distinctly expanded DPPG monolayers by both chitosan insertion within the lipid monolayer and by interacting with the anionic head group. Therefore, PBS buffer can be used as a subphase for more biologically relevant studies of chitosan interactions with Langmuir films, shedding light on why chitosan is antibacterial but not toxic to mammals, as the interaction mechanism depends on lipid headgroup charge.