Impact of the Coating on the Insertion of Magnetite Nanoparticles into Membrane Models

In this study, we investigated the interactions between magnetite (Fe₃O₄) functionalized with either citrate (Fe₃O₄@C) or polyethyl-amino-ethyl cellulose (Fe₃O₄@PQ) and membrane model systems, using Langmuir isotherms and incorporation experiments. Phospholipid monolayers of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycerol-3-phosphate (DSPA), which have the same hydrocarbon chains, were employed as cell membrane models. Magnetite nanoparticles (NPs) were successfully synthesized and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), Fourier-transform infrared spectroscopy (FTIR), and zeta potential analyses. Both surface pressure vs time incorporation experiments and compression isotherms revealed favorable interactions between the NPs and the lipid monolayers. We also evaluated the influence of the initial surface pressure of the monolayer to determine the maximum insertion pressure (MIP). At low concentrations, the NPs with both types of coatings expanded the monolayers due to area exclusion effects, while at higher concentrations, they promoted the formation of 3D structures. Fe₃O₄@PQ exhibited stronger initial interactions with the lipid films, particularly with DSPC, likely due to enhanced hydrophobic and electrostatic interactions. However, Brewster angle microscopy imaging and insertion experiments revealed that Fe₃O₄@C penetrate more effectively into the monolayers. In addition, the impact of using fresh versus aged NP dispersions was assessed. Aged NP dispersions caused greater structural disruption and reduced film rigidity, underscoring the importance of using fresh nanoparticle suspensions to ensure reproducibility. All systems displayed MIP values above 30 mN/m, exceeding physiological membrane pressures and suggesting that the NPs with both types of coatings are capable of penetrating biological membranes. Overall, Fe₃O₄@C demonstrated higher insertion efficiency and time-dependent penetration rate values (V_MAX) under all conditions, highlighting the crucial role of surface chemistry in modulating nanoparticle-membrane interactions. These observations emphasize the significant role of nanoparticle surface chemistry in modulating the structural organization of phospholipid monolayers.