Gold nanoparticles partition to and increase the activity of glucose-6-phosphatase in a synthetic phospholipid membrane system.

Engineered nanomaterials can alter the structure and/or function of biological membranes and membrane proteins but the underlying mechanisms remain unclear. We addressed this using a Langmuir phospholipid monolayer containing an active transmembrane protein, glucose-6-phosphatase (G6Pase). Gold nanoparticles (nAu) with varying ligand shell composition and hydrophobicity were synthesized, and their partitioning in the membrane and effects on protein activity characterized. nAu incorporation did not alter the macroscopic properties of the membrane. Atomic force microscopy showed that when co-spread with other components prior to membrane compression, nAu preferentially interacted with G6Pase and each other in a functional group-dependent manner. Under these conditions, all nAu formulations reduced G6Pase aggregation in the membrane, enhancing catalytic activity 5-6 fold. When injected into the subphase beneath pre-compressed monolayers, nAu did not affect G6Pase activity over 60 minutes, implying they were unable to interact with the protein under these conditions. A small but significant quenching of tryptophan fluorescence showed that nAu interacted with G6Pase in aqueous suspension. nAu also significantly reduced the hydrodynamic diameter of G6Pase in aqueous suspension and promoted catalytic activity, likely via a similar mechanism to that observed in co-spread monolayers. Overall, our results show that nAu can incorporate into membranes and associate preferentially with membrane proteins under certain conditions and that partitioning is dependent upon ligand shell chemistry and composition. Once incorporated, nAu can alter the distribution of membrane proteins and indirectly affect their function by improving active site accessibility, or potentially by changing their native structure and distribution in the membrane.

Cerium oxide nanoparticles exhibit minimal cardiac and cytotoxicity in the freshwater fish Catostomus commersonii.

Metal oxide nanomaterials can cause oxidative, cardiorespiratory, and osmoregulatory stress in freshwater fish. In contrast, cerium oxide nanoparticles (nCeO2) can have antioxidant effects but their aquatic toxicity has not been fully characterized. Heart rate and heart rate variability were followed in white sucker (Catostomus commersonii) acutely exposed to 1.0 mg L(-1) nCeO2 for 25 h. Malondialdehyde (MDA) was measured to assess oxidative tissue damage, and plasma cortisol, glucose, lactate, and osmolality were assessed as indicators of physiological and osmoregulatory stress. There was no MDA accumulation in gill or heart of fish exposed to nCeO2 and heart function was unchanged over the 25 h treatment. Plasma cortisol increased 6-fold but there was no change in plasma glucose or lactate. Cellular osmoregulatory toxicity was studied using an isolated red blood cell (RBC) model. In vitro exposure to 1.0 mg L(-1) nCeO2 for 1h had no effect on cell morphological parameters and did not sensitize RBCs to hemolysis under hypotonic stress. Overall, there were no indications of oxidative, cardiorespiratory, or osmoregulatory stress following acute exposure to nCeO2. Elevated plasma cortisol levels suggest that nCeO2 may exert mild toxicity to tissues outside of the cardiorespiratory system.

Cardiorespiratory toxicity of environmentally relevant zinc oxide nanoparticles in the freshwater fish Catostomus commersonii.

The inhalation of zinc oxide engineered nanomaterials (ENMs) has been linked to cardiorespiratory dysfunction in mammalian models but the effects of aquatic ENM exposure on fish have not been fully investigated. Nano-zinc oxide (nZnO) is widely used in consumer products such as sunscreens and can make its way into aquatic ecosystems from domestic and commercial wastewater. This study examined the impact of an environmentally relevant nZnO formulation on cardiorespiratory function and energy metabolism in the white sucker (Catostomus commersonii), a freshwater teleost fish. Evidence of oxidative and cellular stress was present in gill tissue, including increases in malondialdehyde levels, heat shock protein (HSP) expression, and caspase 3/7 activity. Gill Na(+)/K(+)-ATPase activity was also higher by approximately three-fold in nZnO-treated fish, likely in response to increased epithelial permeability or structural remodeling. Despite evidence of toxicity in gill, plasma cortisol and lactate levels did not change in animals exposed to 1.0 mg L(-1) nZnO. White suckers also exhibited a 35% decrease in heart rate during nZnO exposure, with no significant changes in resting oxygen consumption or tissue energy stores. Our results suggest that tissue damage or cellular stress resulting from nZnO exposure activates gill neuroepithelial cells, triggering a whole-animal hypoxic response. An increase in parasympathetic nervous signaling will decrease heart rate and may reduce energy demand, even in the face of an environmental toxicant. We have shown that acute exposure to nZnO is toxic to white suckers and that ENMs have the potential to negatively impact cardiorespiratory function in adult fish.