ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels

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.Electronic supplementary materialThe online version of this article (10.1186/s12951-017-0327-9) contains supplementary material, which is available to authorized users.

Lysenin Channels as Sensors for Ions and Molecules

“…Consequently, monovalent anions and cations do not modulate the channel's conductance other than by adjusting the electrolyte solution's conductivity [53,62]. which different chemicals modulate the channel's conductance depend on the physical properties and chemical identities of analytes, and include simple binding and partial occlusion, conformational changes to closed or sub-conducting states (ligand-induced gating), and gating and trapping of long polymeric molecules [58][59][60][61][62]. In the same line of sensing capabilities, the large opening of lysenin channels and absence of vestibular constrictions recommends them as analytical tools for single molecule detection and characterization by resistive pulse techniques (stochastic sensing) [29,51,58].…”

“…However, two other salient features suggest the potential use of lysenin channels as powerful analytical tools, and these are the major focus of this informative review. Lysenin presents binding sites for multivalent cations and anions; when such compounds are used as analytes, lysenin channels respond by diminishing their conductance proportionally to the concentration of the chemical stimulus [58][59][60][61][62][63]. In most cases, the response is reversible and ligand removal leads to complete restoration of the channel's conducting properties.…”

Interactions of nanomaterials with ion channels and related mechanisms

“…The decrease in the macroscopic conductance was asymmetrical with respect to electrostatic interactions between ZnO NPs and a potential binding site. Conversely, no inhibitory effects were observed for anionic SnO 2 NPs (Bryant et al, 2017). (Gavello et al, 2012).…”

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

“…Accurately predicting the catalytic role of active proteins interacting with nanostructures is an open field for molecular simulation techniques. Intervening in active and regulatory transport systems can, however, easily show the fate of over-ambition: A nanomaterial that perturbs active machineries such as glucose or ion transporters, 30,31 or active lipid exchangers between leaflets, may cause unpredictable regulatory failures and toxic effects.…”