Impacts Of Iron Oxide Nanoparticles On Model Cell Membranes By Adjusting The Membrane Charges And Membrane Components

Iron oxide nanoparticles(NPs)and their composites are excellent adsorbents and catalysts.Due to their superparamagnetism and good biocompatibility,magnetic iron oxide NPs can be functionally modified and are widely used in various fields of biomedicine.The universal and diverse application of iron oxide NPs greatly increases the possibility of direct contact of NPs with biological interfaces.Therefore,studying the interactions of iron oxide NPs with biological interfaces is necessary to evaluate its safety to organism.Real cell membranes have various components,complex structures,hence they are asymmetric and laterally heterogenetic.Moreover,the overall zeta potential of the membrane is negative but it contains a small amount of positively charged domains.These components and structural properties are closely related to NP-membrane interactions.Therefore,in this study,giant unilamellar vesicles(GUVs)and small unilamellar vesicles(SUVs)were chosen as model cell membranes.The charge distribution and the lipid composition of real cell membranes were simulated by adjusting the amount of charged lipids(cationic lipid DOTAP and anionic lipid DOPG)and introducing different lipids,such as phosphatidylethanolamine(PE),phosphatidylserine(PS),sphingomyelin(SM),and cholesterol(Chol).The effects of ?-Fe2O3 NPs on the morphology and integrity of model cell membranes were studied by laser scanning confocal microscopy and quartz crystal microbalance(QCM)technology.The alteration of the membrane fluidity induced by NPs were quantitatively analyzed by fluorescence spectra and the generalized polarization values.Moreover,the changes of lipid moleculuar structures caused by NPs were analyzed by comparing their infrared spectra.Positively charged sites play an important role in the NP-membrane interactions.Microscopic observation and QCM experiments showed that when the model cell membranes were overall negatively charged with few positively charged sites,y-Fe2O3 NPs could adhere to the membranes and even cause membrane rupture.That is,the positively charged sites on model cell membranes provide sites for the adhesion of y-Fe2O3 NPs.Compared with the overall membrane zeta potential,the number of positively charged sites in the membrane determines the degree of membrane damage caused by y-Fe2O3 NPs.In addition,the lipid order of SUVs decreased after exposure to ?-Fe2O3 NPs,the membrane fluidity therefore increased.The infrared spectra showed that ?-Fe2O3 NPs could interact with the membrane through phosphodiester and trimethylamine groups of lipid molecules.Different lipid species in the membrane also cause differences in the NP-membrane interactions.QCM experiments showed that although the SUVs were overall negatively charged,the NP-membrane interactions were different for SUVs with different lipid compositions.When SM or Chol was present in the membrane,?-Fe2O3 NPs could approach the membrane via free diffusion and cause obvious NP adhesion or even membrane rupture.When SM and Chol were simultaneously present in the membrane,Chol could form a liquid-ordered(Lo)domain with SM.The presence of this membrane domain could weaken the NP-membrane interaction and enhance the membrane stability.In addition,the presence of the Lo domain maintained the fluidity of the membrane and inhibited the increase in membrane fluidity induced by ?-Fe2O3 NPs.The infrared spectra showed that ?-Fe2O3 NPs could interact with the membrane through amide groups and hydroxyl groups of SM and Chol molecules.Moreover,when the positively charged sites and lipid components were simultaneously introduced into the model cell membranes,the QCM experiments and GP value calculations showed that the,?-Fe2O3 NP-membrane interactions were enhanced,and the NP adhesion on the membrane was increased,which might even cause membrane rupture.This may be because the membrane contained not only positively charged sites,but also rich lipid species.?-Fe2O3 NPs could strongly interact with the membranes by combining various groups of different lipid molecules.This study reveals the possible mechanisms of the interactions between ?-Fe2O3 NPs and model cell membranes.This work provides a basis for predicting the environmental behavior and environmental fate of ?-Fe2O3 NPs,and is crucial for understanding its biological effects and confirm its safety to organism.