Recent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca 2+-sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1ferritin-expressing HEK-293T cells at 30 °C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by ~ 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30-32 °C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (RoS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics. New approaches have been advanced for controlling signal transduction 1 , cell activity, and protein expression 2 with temporal precision, contributing to advances in on-demand biomanufacturing of protein biologics 3 , developing new tools for drug discovery 4 , in vitro expansion and differentiation of stem cells for regenerative medicine 5 , and regulating the activity of neurons and other cell types in vivo 5. One example is optogenetics, which uses precise wavelengths of light to stimulate light sensitive channels 6,7. Alternatively, gold nanorods (AuNRs) can be actuated by near-infrared (NIR) wavelengths to confer light-sensitivity to light-insensitive, heat-sensitive targets. Specifically, antibody-coated AuNRs targeted to transient receptor potential (TRP) vanilloid 1 (TRPV1) cation channels and integrins generated plasmonic heating when stimulated with select wavelengths of NIR light and gated Ca 2+ flux into cells to control cellular functions 8. In each optical technique, the low penetration depth of visible and NIR light into cellular systems limits application either in vitro or in vivo 9. Another example is chemogenetics, in which drug ligands can gate mutated ion channels 10 or G-protein coupled receptors 11. Chemogenetics does not require an implant but is limited by a slow onset of action that is dictated by the pharmacokinetics of the drug actuator in vivo and the addition of a chemical inducer to in vitro cell-based reactors 12. Still other approaches for activating signal transduction have been developed including the use of size-controlled microbubbles targeted to Piezo1 ion channels to gate Ca 2+ flux by ultrasound stimulation 13 and magnetic activation of engineered ion channels 14-18. The use of magnetic fields to gate TRPV1 and related ion channels has been shown in multiple studies. Pralle and co-workers used megahertz radio frequency (RF) alternating magnetic fields (AMFs) to gate TRPV1 when external ...

A hot wire chemical vapor deposition technique is described for synthesis of 1D nanostructures of a controlled morphology, stoichiometry, and composition. The synthesis involves the evaporation and condensation of metal oxide vapor through the reaction of oxygen with the hot filaments of respective transition metals. The stoichiometry and morphology of MoO 3 and WO 3 were modulated by varying the filament temperature and partial pressure of oxygen in the growth chamber. Based on the results under different conditions, a morphological phase diagram, and a growth model based on the extent of gas phase supersaturation were developed to understand the growth mechanism. Further, ternary transition metal oxide, NiMoO 4, was synthesized as a proof-of-concept for tuning the composition of deposition through simultaneous evaporation of two metal oxides.

The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers. By tuning the valency and linker length, we designed polyvalent inhibitors that were over four orders of magnitude more potent than the corresponding monovalent ligands. This strategy for the rational design of monodisperse polyvalent molecules may not only be broadly applicable for the inhibition of toxins and pathogens, but also for controlling the nanoscale organization of cellular receptors to regulate signaling and stem cell fate.

In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.

Electric fields stimulate genetically modified pancreatic β cells to secrete insulin in mice