High-Energy Al/CuO Nanocomposites Obtained by DNA-Directed Assembly

Over the next few years, it is expected that new, energetic, multifunctional materials will be engineered. There is a need for new methods to assemble such materials from manufactured nanopowders. In this article, we demonstrate a DNA-directed assembly procedure to produce highly energetic nanocomposites by assembling Al and CuO nanoparticles into micrometer-sized particles of an Al/CuO nanocomposite, which has exquisite energetic performance in comparison with its physically mixed Al/CuO counterparts. Using 80 nm Al nanoparticles, the heat of reaction and the onset temperature are 1.8 kJ g-1 and 410 degrees C, respectively. This experimental achievement relies on the development of simple and reliable protocols to disperse and sort metallic and metal oxide nanopowders in aqueous solution and the establishment of specific DNA surface-modification processes for Al and CuO nanoparticles. Overall, our work, which shows that DNA can be used as a structural material to assemble Al/Al, CuO/CuO and Al/CuO composite materials, opens a route for molecular engineering of the material on the nanoscale

Nucleosome Chiral Transition under Positive Torsional Stress in Single Chromatin Fibers

Using magnetic tweezers to investigate the mechanical response of single chromatin fibers, we show that fibers submitted to large positive torsion transiently trap positive turns, at a rate of one turn per nucleosome. A comparison with the response of fibers of tetrasomes (the (H3-H4)2 tetramer bound with ~50 bp of DNA) obtained by depletion of H2A-H2B dimers, suggests that the trapping reflects a nucleosome chiral transition to a metastable form built on the previously documented righthanded tetrasome. In view of its low energy, <8 kT, we propose this transition is physiologically relevant and serves to break the docking of the dimers on the tetramer which in the absence of other factors exerts a strong block against elongation of transcription by the main RNA polymerase.Comment: 33 pages (double spacing), 7 figure

Structural plasticity of single chromatin fibers revealed by torsional manipulation

Magnetic tweezers are used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large amount of supercoiling without much change in length. This behavior is quantitatively described by a molecular model of the chromatin 3-D architecture. In this model, we assume the existence of a dynamic equilibrium between three conformations of the nucleosome, which are determined by the crossing status of the entry/exit DNAs (positive, null or negative). Torsional strain, in displacing that equilibrium, extensively reorganizes the fiber architecture. The model explains a number of long-standing topological questions regarding DNA in chromatin, and may provide the ground to better understand the dynamic binding of most chromatin-associated proteins.Comment: 18 pages, 7 figures, Supplementary information available at http://www.nature.com/nsmb/journal/v13/n5/suppinfo/nsmb1087_S1.htm

Motion analysis of chromosomes in budding yeast: DNA, chromatin, and chromosomes under the microscope

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Technologies for genomic and epigenomic analysis: a new frontier for micro- and nano-fluidics

Biology has become a mainstream field of research, fostering interactions between scientists specialized in physics, technology, and mathematics. The complexity of biological systems is full of challenges that can only be elucidated with the development of multiple techniques dedicated to the characterization of biological transactions. These transactions involve molecular interactions, which in turn may trigger signals at the body level, hence defining multi-scale scientific problems. In addition to scientific challenges, modern questions of the life sciences are expected to stimulate innovations to fulfill the growing demand for personalized diagnostics. Micro- and nano-technologies offer new solutions to manipulate and sense single cells or molecules with exquisite precision. Their complementarity with respect to conventional molecular biology techniques, which enable to characterize biological compounds at the batch level, is well established, yet their impact in molecular/cellular biology practices were disappointing compared to initial anticipations. Starting from our own research at the frontiers of physics and biology, we will try to identify opportunities for future developments in micro- and nano-technologies for life sciences. We will then propose projects focused on single cell whole-genome analysis that have retained our attention.Les sciences de la vie et de la santé sont aujourd'hui au centre d'intérêts scientifiques et économiques. Les aspects économiques sont présidés par le développement de nouveaux outils de diagnostic fiables, reposant sur des mesures parallélisées d'interaction moléculaires au niveau de l'ADN ou des protéines. L'intérêt scientifique est très pluridisciplinaire, car les mécanismes de la vie impliquent des réactions physico-physiques multiples, que l'on aborde avec des technologies nouvelles et des approches de modélisation encore à développer. Dans ce panorama, les micro- et nano-technologies sont appelées à apporter de nouvelles solutions car elles permettent de manipuler des cellules ou des molécules avec une grande précision temporelle et spatiale. Elles sont en outre complémentaires avec les outils classiques de la biologie cellulaire et moléculaire, qui permettent des analyses sur des échantillons de grande dimension. Pourtant les exemples de succès scientifiques à l'interface des sciences de la vie et de la biologie restent plutôt rares. Dans ce manuscrit, nous faisons un tour d'horizon sur l'émergence de nouvelles technologies dédiées à l'analyse du génome. Nous présentons certaines de nos contributions, et proposons quelques pistes pour de futures recherches, principalement focalisées sur l'étude des mécanismes d'instabilité du génome réalisée dans des populations contenant seulement quelques cellules

Conformation and dynamics of DNA in confined environments: cross-talk between chromosomes in live cells and nanofluidic technologies

International audienceGenome structure and dynamics attacts considerable attention in the biology community to eludicate genome regulation principles, but also for biological physicists who aim to develop models of DNA in vivo. The challenges of this research is conceptual but also economical because of expected impact of DNA sequencing or DNA microarrays technologies in personalized diagnostics. Our research is carried out at the nexus of technology and biology and aims to provide a physical description of the genome structural properties. We will first overview our results on chromosome dynamics in living yeast, showing the unexpected flexibility of these structures in vivo. We will then focus on new methods for chromosome analysis in vitro based on micro- and nano-fluidics, and we will finally emphasize that that these two topics are not so unrelated, given that the physics of DNA confined environment can be used as a common research framework

High sensitivity detection of DNA with microfluidics: transfer of a technology dedicated to the profiling of circulating DNA

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Relevance of fractal and polymer models to describe nuclear architecture Is a unified picture out of reach?

International audienceChromosome architecture plays an essential role for all nuclear functions, and its physical description has attracted considerable interest over the last few years among the biophysics community. These researches at the frontiers of physics and biology have been stimulated by the demand for quantitative analysis of molecular biology experiments, which provide comprehensive data on chromosome folding, or of live cell Imaging experiments that enable researchers to visualize selected chromosome loci in living or fixed cells. In this review our goal is to survey several nonmutually exclusive models that have emerged to describe the folding of DNA in the nucleus, the dynamics of proteins in the nucleoplasm, or the movements of chromosome loci. We focus on three classes of models, namely molecular crowding, fractal, and polymer models, draw comparisons, and discuss their merits and limitations in the context of chromosome structure and dynamics, or nuclear protein navigation in the nucleoplasm. Finally, we identify future challenges in the roadmap to a unified model of the nuclear environment

Deformation but not convection induced by intraluminal pressure enhances transport through barrier tissues

International audienceendothelial or epithelial tissues form semipermeable barriers that restrict and regulate the transport of solutes to their surrounding tissues. Microphysiological systems aim to recapitulate this hallmark function and provide models for e.g. drug screening. Here, we develop, and validate by extensive simulations, two assays dedicated to the characterization of diffusion- and pressure-driven transport across epithelial and endothelial ductal tissues fabricated in collagen matrices. We first prove that, upon pressure actuation, barrier crossing is enhanced, although transport in paracellular space remains dominated by diffusion. Using the monopore model, we show that diffusion-driven measurements are consistent with paracellular pore radii of 2.1 and 24 nm for epithelial and endothelial tissues, respectively, but also demonstrate that these estimates fail to account for pressure-driven transport data. We solve this contradiction by introducing the deformable monopore model, which assumes the same pore sizes of 2.1 and 24 nm, and includes the deformation, essentially elongational thinning of paracellular cleft, induced by intraluminal stress to fit pressure-driven transport. Hence, this study suggests that transport through barrier tissues can be regulated by mechanical strai