The nanoscale engineering of nucleic acids has led to exciting molecular technologies for high-end biological imaging. The predictable base pairing, high programmability, and superior new chemical and biological methods used to access nucleic acids with diverse lengths and in high purity, coupled with computational tools for their design, have allowed the creation of a stunning diversity of nucleic acid--based nanodevices. Given their biological origin, such synthetic devices have a tremendous capacity to interface with the biological world, and this capacity lies at the heart of several nucleic acid--based technologies that are finding applications in biological systems. We discuss these diverse applications and emphasize the advantage, in terms of physicochemical properties, that the nucleic acid scaffold brings to these contexts. As our ability to engineer this versatile scaffold increases, its applications in structural, cellular, and organismal biology are clearly poised to massively expand.
The role of membrane potential in most intracellular organelles remains unexplored because of the lack of suitable tools. Here, we describe a fluorescent DNA-nanodevice that reports absolute membrane potential and can be targeted to organelles in live cells. This nanodevice, denoted
Voltair
, bears a voltage-sensitive fluorophore, a reference fluorophore for ratiometry, and acts as an endocytic tracer. Using
Voltair
we could measure the membrane potential of different organelles
in situ
in live cells.
Voltair
can potentially guide the rational design of biocompatible electronics as well as expand our understanding of how membrane potential regulates organelle biology.
Cellular reporters of enzyme activity are based on either fluorescent proteins or small molecules. Such reporters provide information corresponding to wherever inside cells the enzyme is maximally active and preclude minor populations present in sub-cellular compartments. Here we describe a chemical imaging strategy to selectively interrogate minor, sub-cellular pools of enzymatic activity. This new technology confines the detection chemistry to a designated organelle, enabling imaging of enzymatic cleavage exclusively within the organelle. We have thus quantitatively mapped disulfide reduction exclusively in endosomes in C. elegans and identified that exchange is mediated by minor populations of enzymes PDI-3 and TRX-1 resident in endosomes. Impeding intra-endosomal disulfide reduction by knocking down TRX-1 protects nematodes from infection by Corynebacterium diphtheriae, revealing the importance of this minor pool of endosomal TRX-1. TRX-1 also mediates endosomal disulfide reduction in human cells. A range of enzymatic cleavage reactions in organelles are amenable to analysis by this new reporter strategy.Minor populations of proteins and protein complexes perform critical functions for the cell. For example, a minor population of the epidermal growth factor receptor present on exosomes mediates intercellular communication 1 . A small fraction of mammalian target of rapamycin, present on lysosomes is responsible for nutrient sensing by the cell 2 . A minor population of the KDEL receptor present in the Golgi apparatus performs the critical function of retrieving ER-resident proteins from the Golgi apparatus 3 . Small molecules that function as fluorescent reporters of enzymatic activity use highly specific and rapid Reprints and permission information is available online at www.nature.com/reprints.
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