The role of positively charged sites in the interaction between model cell membranes and γ-FeO NPs.

The various applications of iron oxide nanoparticles (NPs) in clinical care and wastewater treatment are rapidly developing, thus their biological safety is worth attention. The electrostatic interaction between cell membranes and NPs is the key mechanism behind membrane damage and membrane penetration. Cell membranes are generally negatively charged with a few positively charged domains. The role of the positively charged sites in the NP-membrane interaction needs further investigation. In this study, the ratio of the positively charged sites was adjusted in two model cell membranes: giant and small unilamellar vesicles (GUVs and SUVs). After exposure to negatively charged γ-Fe2O3 NPs, the adhesion of NPs on the membranes and the induced membrane disruption were studied by microscopic observation and quartz crystal microbalance (QCM) monitoring. γ-Fe2O3 NPs adhered to and disrupted the membranes containing even few positively charged sites, although the whole membrane exhibited a negative zeta potential and hence electrostatically repels the NPs. The number of adhered γ-Fe2O3 NPs increased remarkably on membranes with overall positive zeta potential, but more serious disruption happened to membranes with higher ratios of positively charged sites. Therefore, the membrane rupture was more correlated to the number of positively charged sites than to the zeta potential of the whole membrane. In addition, exposure to γ-Fe2O3 NPs decreased the order of the lipid molecules and hence increased the fluidity of the membrane phase, and the most significant phase change occurred in the negatively charged membrane with the highest ratio of positively charged sites. Infrared spectra indicated that γ-Fe2O3 NPs probably interact with the membranes via the phosphodiester and trimethylamine groups in the lipid head groups. Our research furthers our knowledge of the electrostatic interaction between NPs and cell membranes, which should help to predict the biological effects of γ-Fe2O3 NPs.