36 research outputs found

    Dynamics of Ion Beam Stimulated Surface Mass Transport to Nanopores

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    ABSTRACT We explore the ion beam-induced dynamics of the formation of large features at the edges of nanopores in freestanding silicon nitride membranes. The shape and size of these ìnanovolcanoesî, together with the rate at which the nanopores open or close, are shown to be strongly influenced by sample temperature. Volcano formation and pore closing slow and stop at low temperatures and saturate at high temperatures. Nanopore volcano size and closing rates are dependent on initial pore size. We discuss both surface diffusion and viscous flow models in the context of these observed phenomena

    Regulation of Mitochondrial Respiration by VDAC Is Enhanced by Membrane-Bound Inhibitors with Disordered Polyanionic C-Terminal Domains

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    The voltage-dependent anion channel (VDAC) is the primary regulating pathway of water-soluble metabolites and ions across the mitochondrial outer membrane. When reconstituted into lipid membranes, VDAC responds to sufficiently large transmembrane potentials by transitioning to gated states in which ATP/ADP flux is reduced and calcium flux is increased. Two otherwise unrelated cytosolic proteins, tubulin, and α-synuclein (αSyn), dock with VDAC by a novel mechanism in which the transmembrane potential draws their disordered, polyanionic C-terminal domains into and through the VDAC channel, thus physically blocking the pore. For both tubulin and αSyn, the blocked state is observed at much lower transmembrane potentials than VDAC gated states, such that in the presence of these cytosolic docking proteins, VDAC’s sensitivity to transmembrane potential is dramatically increased. Remarkably, the features of the VDAC gated states relevant for bioenergetics—reduced metabolite flux and increased calcium flux—are preserved in the blocked state induced by either docking protein. The ability of tubulin and αSyn to modulate mitochondrial potential and ATP production in vivo is now supported by many studies. The common physical origin of the interactions of both tubulin and αSyn with VDAC leads to a general model of a VDAC inhibitor, facilitates predictions of the effect of post-translational modifications of known inhibitors, and points the way toward the development of novel therapeutics targeting VDAC

    Pressure-Controlled Motion of Single Polymers through Solid-State Nanopores. Nano Lett

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    ABSTRACT: Voltage-biased solid-state nanopores are well established in their ability to detect and characterize single polymers, such as DNA, in electrolytes. The addition of a pressure gradient across the nanopore yields a second molecular driving force that provides new freedom for studying molecules in nanopores. In this work, we show that opposing pressure and voltage bias enables nanopores to detect and resolve very short DNA molecules, as well as to detect near-neutral polymers
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