In situ kinase profiling reveals functionally relevant properties of native kinases

Protein kinases are intensely studied mediators of cellular signaling, yet important questions remain regarding their regulation and in?vivo properties. Here, we use a probe-based chemoprotemics platform to profile several well studied kinase inhibitors against >200 kinases in native cell proteomes and reveal biological targets for some of these inhibitors. Several striking differences were identified between native and recombinant kinase inhibitory profiles, in particular, for the Raf kinases. The native kinase binding profiles presented here closely mirror the cellular activity of these inhibitors, even when the inhibition profiles differ dramatically from recombinant assay results. Additionally, Raf activation events could be detected on live cell treatment with inhibitors. These studies highlight the complexities of protein kinase behavior in the cellular context and demonstrate that profiling with only recombinant/purified enzymes can be misleading.     

Integration of an Axially Continuous Graphene with Functional Metals for High-Temperature Electrical Conductors

Demands for effective high-temperature electrical conductors continue to increase with the rapid adoption of electric vehicles. However, the use of conventional copper-based conductors is limited to relatively low temperatures due to their poor oxidation resistance and microstructural instability. Here, a highly conductive and thermally stable nickel-graphene-copper (NiGCu) wire that combines the advantages of graphene and its metallic components is developed. The NiGCu wire consists of a conductive copper core, an oxidation-resistant nickel shell, and axially continuous graphene embedded between them. The experiments on 10–80 µm diameter NiGCu wires demonstrate substantial enhancements in electrical properties and thermal stability across a variety of metrics. For instance, the smallest NiGCu wires have a 61.2% higher current density limit, 307.6% higher conductivity, and an order of magnitude smaller change in resistivity compared to conventional Ni-coated Cu counterparts after annealing at 650 °C. By performing both innovative experiments and simulations using different sizes of NiGCu wires, the diffusion coefficients of metals are quantified, for the first time to the best knowledge, through continuous graphene. These results indicate that the dramatic improvement in thermo-electrical properties is enabled by the embedded graphene layer which reduces Ni Cu interdiffusion by ≈10⁴ times at 550 °C and 650 °C.