HypothesisThe activity of submicron sized titanium oxide (TiO2) particles towards biomembrane models is coupled to their charge carrying capacity and their primary particle size.ExperimentsElectrochemical methods using a phospholipid layer on mercury (Hg) membrane model have been used to determine the phospholipid monolayer activity of TiO2 as an indicator of biomembrane activity. The particles were characterised for size, by dynamic light scattering (DLS) and scanning electron microscopy (SEM), and for charge, by acid-base titration.FindingsTiO2 nanoparticles aggregate in 0.1 mol dm−3 solutions of KCl. The charge capacity of TiO2 nanoparticles depends on their primary particle size and is unaffected by aggregation. TiO2 particles of ∼40 nm primary particle size interact significantly with phospholipid layers. Aggregation of these particles initially has a small effect on this interaction but long term aggregation influences the interaction whereby the aggregates penetrate the lipid layer rather than adsorbing on the surface. Fulvic acid does not inhibit the ∼40 nm particle/phospholipid interaction.P25 TiO2 particles of larger particle size interact less strongly with phospholipid layers and the interaction is alleviated following particle aggregation. The semiconductor properties of TiO2 are evident in voltammograms showing electron transfer to TiO2 adsorbed on uncoated Hg.

•We examine the interaction between ZnO nanoparticles and phospholipid monolayers.•A phospholipid coated fabricated Pt/Hg microelectrode in flow system is used.•Rapid cyclic voltammetry is employed to monitor the extent of interaction.•The ZnO–phospholipid interaction is inversely related to ZnO particle size.•Larger particles disrupt the layer and instigate electron transfer from Hg to ZnO.Aqueous ZnO nanoparticle dispersions interaction with a dioleoyl phosphatidylcholine (DOPC) monolayer is reported in this paper. ZnO-DOPC interactions were investigated using rapid cyclic voltammetry (RCV) by focusing on the effect of the interactions on the characteristics of the capacitance current peaks representing two potential induced phase transitions. Results showed: – (1) The order of interaction of common commercially sourced nanoparticles with DOPC coated Hg electrodes was NanoTek > NanoShield > metals basis. This extent of interaction was inversely related to the ZnO particle size where the metals basis nanoparticles were strongly aggregated. The contribution of the non-ionic dispersant added by manufacturer to the NanoTek and NanoShield interaction was uncertain. (2) Freshly prepared aqueous Nanosun ZnO nanoparticle (∼25 nm) dispersions interacted with and penetrated DOPC coated Hg electrodes. Aggregation of the nanoparticles, coating of the ZnO with phosphate and coating of the ZnO with fulvic acid minimised ZnO–DOPC interaction. (3) In-house synthesised ZnO nanoparticles of lower primary particle size (∼6 nm) than Nanosun ZnO nanoparticles interacted strongly with DOPC coated Hg electrodes with no evidence of penetration of the nanoparticle in the DOPC monolayer. Even after considerable aggregation of the particle to between 1 and 10 μm, a strong interaction of the in-house synthesised ZnO with DOPC was observed.Graphical abstract

To test the biocompatible character of room-temperature ionic liquids (ILs), the interaction of various ILs with biological membrane (biomembrane) models was studied in this work. Dioleoyl phosphatidylcholine (DOPC) adsorbed on a mercury (Hg) electrode forms an impermeable defect-free monolayer which is a well established biomembrane model, prone to be studied by electrochemical techniques. We have monitored the modifications of the Hg supported monolayer caused by ILs using rapid cyclic voltammetry (RCV), alternating current voltammetry (ACV), and electrochemical impedance spectroscopy (EIS). A series of imidazolium-based ILs were investigated whose interaction highlighted the role of anion and lateral side chain of cation during the interaction with DOPC monolayers. It was shown that the hydrophobic and lipophilic character of the IL cations is a primary factor responsible for this interaction. Hg-supported monolayers provide an accurate analysis of the behavior of ILs at the interface of a biomembrane leading to a comprehensive understanding of the interaction mechanisms involved. At the same time, these experiments show that the Hg-phospholipid model is an effective toxicity sensing technique as shown by the correlation between literature in vivo toxicity data and the data from this study.

Understanding the interactions between nanoparticles (NPs) and biological matter is a high-priority research area because of the importance of elucidating the physical mechanisms underlying the interactions leading to NP potential toxicity as well as NP viability as therapeutic vectors in nanomedicine. Here, we use two model membrane systems, giant unilamellar vesicles (GUVs) and supported monolayers, to demonstrate the competition between adhesion and elastic energy at the nanobio interface, leading to different mechanisms of NP–membrane interaction relating to NP size. Small NPs (18 nm) cause a “freeze effect” of otherwise fluid phospholipids, significantly decreasing the phospholipid lateral mobility. The release of tension through stress-induced fracture mechanics results in a single microsize hole in the GUVs after interaction. Large particles (>78 nm) promote membrane wrapping, which leads to increased lipid lateral mobility and the eventual collapse of the vesicles. Electrochemical impedance spectroscopy on the supported monolayer model confirms that differently sized NPs interact differently with the phospholipids in close proximity to the electrode during the lipid desorption process. The time scale of these processes is in accordance with the proposed NP/GUV interaction mechanism.

A sensing system for the rapid on-line screening of lipids and biomembrane active compounds in water samples has been successfully developed. The sensor consists of a flow cell and incorporated wafer-based device with on-chip mercury on platinum (Pt/Hg) working electrode and platinum (Pt) auxiliary and pseudo-reference electrodes. To optimise system performance, the following experiments were carried out: (i) Deposition and removal of phospholipid layers on and from Pt/Hg electrodes respectively, (ii) Effect of electrode size on signal, (iii) Monitoring of different phospholipids deposited in flow cell and, (iv) Detection of phospholipid monolayer interaction with representative compounds. The results showed that: (i) Miniaturisation and ruggedisation of the mercury (Hg)/phospholipid system has been successfully achieved, (ii) Rapid cyclic voltammetry facilitates repetitive dioleoyl phosphatidylcholine (DOPC) monolayer formation on Hg from aqueous DOPC dispersion and, (iii) The device responds selectively to organic compounds injected into electrolyte flow.

•Substituted biphenyls (BP) interact with DOPC membranes in the order p- > m- > o-.•Substituents modulate the penetration of BPs into DOPC membranes.•BP substituent position and ring polarizability influence BP/membrane interaction.•Monolayer/bilayer experiments give consistent results for BP/membrane interaction.Electrochemical impedance techniques and fluorescence spectroscopic methods have been applied to the study of the interaction of ortho (o)-, meta (m)- and para (p)-Cl-, o-, m- and p-HO-, p-H3CO-, p-H3C-, p-NC- and p-O3− S- substituted biphenyls (BPs) with Hg supported dioleoyl phosphatidylcholine (DOPC) monolayers and DOPC vesicles. Non-planar o-substituted BPs exhibit the weakest interactions whereas planar p-substituted BPs interact to the greatest extent with the DOPC layers. The substituted BP/DOPC monolayer and bilayer interaction depends on the effect of the substituent on the aromatic electron density, which is related to the substituents' mesomeric Hammetts constants. Substituted BPs with increased ring electron density do not increase the DOPC monolayer thickness on Hg and penetrate the DOPC vesicle membranes to the greatest extent. Substituted BPs with lower ring electron density can cause an increase in the monolayer's thickness on Hg depending on their location and they remain in the interfacial and superficial layer of the free standing DOPC membranes. Quantum mechanical calculations correlate the binding energy between the substituted BP rings and methyl acetate, as a model for the –CH2-(CO)O-CH2- fragment of a DOPC molecule, with the location of BPs within the DOPC monolayer.