Abstract
BackgroundThe insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate.ResultsThe macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO2 NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels.ConclusionWe conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization.
Highlights
The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications
Once a steady state current through the population of lysenin channels was achieved, the NPs were introduced into either side of the chamber with both negative and positive voltages applied across the membrane to assess their effect on the macroscopic conductance
If conductance inhibition elicited by ZnO NPs had been induced by the Zn2+ ions dissipating from the NPs, addition to either side would have displayed a similar pattern of conductance inhibition
Summary
The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. Studies on ZnO NPs have demonstrated toxicity towards a large number of cell lines and model organisms, the mechanism of cytotoxicity is still under debate Certain physicochemical properties, such as surface chemistry, dissolution potential, and their intrinsic ability to produce reactive oxygen species (ROS) have a strong impact on their cytotoxic effects [19,20,21]. Similar to other NPs, the crystal and hydrodynamic size of S nO2 NPs play an important role on their toxic effects, and smaller sizes have been shown to correlate with increased toxicity [27]
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