Interparticle friction leads to non-monotonic flow curves and hysteresis in viscous suspensions

Hysteresis is a major feature of the solid-liquid transition in granular materials. This property, by allowing metastable states, can potentially yield catastrophic phenomena such as earthquakes or aerial landslides. The origin of hysteresis in granular flows is still debated. However, most mechanisms put forward so far rely on the presence of inertia at the particle level. In this paper, we study the avalanche dynamics of non-Brownian suspensions in slowly rotating drums and reveal large hysteresis of the avalanche angle even in the absence of inertia. By using micro-silica particles whose interparticle friction coefficient can be turned off, we show that microscopic friction, conversely to inertia, is key to triggering hysteresis in granular suspensions. To understand this link between friction and hysteresis, we use the rotating drum as a rheometer to extract the suspension rheology close to the flow onset for both frictional and frictionless suspensions. This analysis shows that the flow rule for frictionless particles is monotonous and follows a power law of exponent $\alpha \!= \! 0.37 \pm 0.05$, in close agreement with the previous theoretical prediction, $\alpha\!=\! 0.35$. By contrast, the flow rule for frictional particles suggests a velocity-weakening behavior, thereby explaining the flow instability and the emergence of hysteresis. These findings show that hysteresis can also occur in particulate media without inertia, questioning the intimate nature of this phenomenon. By highlighting the role of microscopic friction, our results may be of interest in the geophysical context to understand the failure mechanism at the origin of undersea landslides.Comment: 10 pages, 8 figure

Synergy of the antibiotic colistin with echinocandin antifungals in Candida species.

International audienceOBJECTIVES: Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. METHODS: A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. RESULTS: We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. CONCLUSIONS: These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins

β(1,3)-Glucanosyl-Transferase Activity Is Essential for Cell Wall Integrity and Viability of Schizosaccharomyces pombe

13 páginas, 7 figuras, 2 tablas.[Background]: The formation of the cell wall in Schizosaccharomyces pombe requires the coordinated activity of enzymes involved in the biosynthesis and modification of b-glucans. The b(1,3)-glucan synthase complex synthesizes linear b(1,3)- glucans, which remain unorganized until they are cross-linked to other b(1,3)-glucans and other cell wall components. Transferases of the GH72 family play important roles in cell wall assembly and its rearrangement in Saccharomyces cerevisiae and Aspergillus fumigatus. Four genes encoding b(1,3)-glucanosyl-transferases -gas1+, gas2+, gas4+ and gas5+- are present in S. pombe, although their function has not been analyzed. [Methodology/Principal Findings]: Here, we report the characterization of the catalytic activity of gas1p, gas2p and gas5p together with studies directed to understand their function during vegetative growth. From the functional point of view, gas1p is essential for cell integrity and viability during vegetative growth, since gas1D mutants can only grow in osmotically supported media, while gas2p and gas5p play a minor role in cell wall construction. From the biochemical point of view, all of them display b(1,3)-glucanosyl-transferase activity, although they differ in their specificity for substrate length, cleavage point and product size. In light of all the above, together with the differences in expression profiles during the life cycle, the S. pombe GH72 proteins may accomplish complementary, non-overlapping functions in fission yeast. [Conclusions/Significance]: We conclude that b(1,3)-glucanosyl-transferase activity is essential for viability in fission yeast, being required to maintain cell integrity during vegetative growth.This research was supported by grants from the Comision Interministerial de Ciencia y Tecnologia (BFU2004-00778) and Junta de Castilla y Leon (GR231) to C.R.V-A and from the European Community (LSHB-CT-2004-511952) to C.R.V-A. and J.P.L. M.M-R. held a fellowship from the Ministerio de Educacion y Ciencia.Peer reviewe

Rhéoépaississement des suspensions denses : mise en évidence de la transition frictionnelle

Shear thickening is a spectacular phenomenon which takes place in some dense suspensions. It manifests itself by a brutal increase of the suspension's viscosity above a certain critical stress. The most iconic example of shear-thickening suspensions is cornstarch and water mixes. Shear thickening long remained a mystery, until recent theoretical and numerical works which proposed a consistent microscopic model. This model explains the shear thickening transition as a frictional one due to the presence of a repulsive force between the grains.During my PhD, I provided one of the first direct experimental proofs of this mechanism. Inspired by granular physics, I showed that shear-thickening suspensions possess a frictionless flowing state at low granular pressure, which is consistent with the proposed model. I then evidenced the frictional transition with controlled experiments using suspensions of silica beads in ionic solutions. To do this, I developed new rheological techniques enabling pressure imposed measurements. Indeed, standard rheological tools do not allow access to the frictional properties of suspensions. The only rheometer that does that is not adapted to the suspensions we study here, which are colloidal. This work thus paves the way for the development of a new generation of pressure imposed rheometers, giving access to colloidal suspensions friction, which is a major challenge in complex fluids rheology.Le rhéoépaississement est un phénomène spectaculaire apparaissant dans certaines suspensions concentrées en particules. Il se manifeste par l’augmentation brutale de la viscosité de la suspension au delà d’une contrainte critique. L’exemple emblématique de suspension présentant ce type de comportement est le mélange d’amidon de maïs et d’eau. Le rhéoépaississement est longtemps resté une énigme, jusqu’à des travaux théoriques et numériques récents proposant un modèle microscopique cohérent. Selon celui-ci, le rhéoépaississement provient d’une transition frictionnelle due à la présence d’une force répulsive entre les grains. Au cours de ma thèse, j’ai réalisé une des premières démonstrations expérimentales directe de ce mécanisme. En m'inspirant de travaux venant du domaine des milieux granulaires, j'ai montré qu'en accord avec le modèle de transition frictionnelle, une suspension rhéoépaississante possède à faible pression granulaire un état non frottant. J'ai ensuite mis en évidence la transition en elle-même dans des suspensions contrôlées de billes de silice dans des solutions salines. Pour cela, j'ai dû développer de nouvelles méthodes de rhéologie à pression imposée. En effet, les rhéomètres standard ne permettent pas d'accéder aux propriétés de frottement des suspensions. Le seul rhéomètre qui le permet n'est pas adapté aux suspensions étudiées ici, qui sont constituées de particules colloïdales. Ce travail ouvre donc la voie au développement d’une nouvelle génération de rhéomètres permettant de mesurer le frottement dans les suspensions colloïdales, un enjeu majeur pour la rhéologie des fluides complexes

Développement de ligands de protéines par assemblage combinatoire autour d'un coeur de rheniumV (application à la cyclophiline hCyp-18)

Cette thèse décrit une nouvelle stratégie pour le développement de composés organométalliques bioactifs, reposant sur l'assemblage combinatoire de sous-chimiothèques (A et B) indépendantes mais complémentaires et capables de coordiner un cœur métallique M, pour former des complexes A-M-B ligands potentiels de biomolécules. La coordination des métaux, bien adaptée à la production de diversité moléculaire est couramment utilisée en chimie médicinale, en médecine nucléaire diagnostique et thérapeutique. Parmi les éléments utilisables, le rhénium et le technétium sont des métaux de choix pour le développement notre stratégie d'assemblage en raison de leurs propriétés chimiques et radiochimiques et de l'analogie de structure de leurs complexes. Notre principal objectif à été de valider cette stratégie in vitro sur une protéine modèle, la cyclophiline hCyp-18 bien connue au laboratoire. C'est une peptidyl-prolyl isomérase reconnaissant principalement des ligands peptidiques ou pseudo-peptidiques, via deux sous-sites fonctionnellement indépendants liant d'une part le résidu proline (sous-site S1-S1') et d'autre part l'extrémité p-nitroanilide (sous-site S2'-S3') des peptides modèles. Nous avons donc développé puis validé in vitro une nouvelle stratégie de synthèse de ligands de protéines par assemblage combinatoire autour du cœur oxorhénium. Nous avons aussi sélectionné de nouveaux ligands de hCyp-18 présentant une meilleure affinité que le peptide de référence Suc-AAPF-pNA. A partir des chimiothèques de modules déjà préparées, nous avons également initié la sélection des ligands de hCyp-18 par chimie combinatoire dynamique.This manuscript describes the development of a novel strategy for the synthesis of organometallic compounds usable as protein ligands, pharmacophores and tracers for molecular imaging through combinatorial assembly of independent modules. Each supramolecular entity is composed of two molecules A and B which are able to coordinate a metal core M in a complementary and unambiguous way to give a metal complex A-M-B. Among a wide variety of metal cores utilized in supramolecular chemistry and nuclear medicine, we selected the oxorhenium and oxotechnetium cores which feature similar interesting chemical and radiochemical properties. The main goal of this work was to validate the strategy in vitro using a model protein, the human cyclophilin hCyp-18, a peptidylprolyl isomerase (PPIases) implicated in numerous biological processes and diseases. Moreover, hCyp-18 possesses two functionally independent subsites which have been thoroughly characterized by NMR, X-ray crystallography and structure activity relationship studies. We developed novel metallated cyclophilin ligands through oxorhenium coordination of independent peptide moieties which reconstitute a canonic PPIase substrate, tetrapeptide Suc-AAPF-pNA. Assembly and biochemical screening of two libraries led to the selection of 2 complexes which exhibit affinities improved by one order of magnitude relative to the reference peptide. Moreover, a Cys-pNA oxorhenium coordinate devoid of proline analog displayed an interesting affinity for cyclophilin. We also initiated the evolutionary selection of cyclophilin ligands via a dynamic combinatorial chemistry.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

The Darcytron: a pressure-imposed device to probe the frictional transition in shear-thickening suspensions

International audienceIn this paper, we present a new device called the Darcytron, allowing pressure-imposed rheological measurements on dense suspensions made of very small particles, like shear-thickening suspensions. The main idea is to impose and control the particle pressure using a vertical Darcy flow across the settled bed of particles. We first validate the proof of concept of the Darcytron on a standard (non shear-thickening) suspension composed of large glass particles. We then use this new device to investigate the frictional behavior of a model shear-thickening suspension composed of small silica particles. These results provide direct evidence of a transition between a frictionless and a frictional state as the particle pressure is increased, providing support to the recent frictional transition scenario for shear thickening

Suspensions rhéo-épaississantes - Principes et applications

International audienceShear-thickening is observed in dense particulate suspensions and consists in a severe increase of the suspension viscosity above an onset stress. This behavior, which is very useful for certain technological applications, can also be an issue in some industrial processes. Shear thickening was considered a puzzle for a long time. It can now be explained as a frictional transition thanks to a recent theoretical model. This paper presents this model and its numerical and experimental validations. Different applications which may emerge from the understanding of this phenomenon are then discussed.Le rhéo-épaississement est un phénomène observé dans certaines suspensions denses de particules. Il consiste en une augmentation parfois brutale de leur viscosité lorsqu'elles sont soumises à une forte contrainte. Ce comportement, très utile pour certaines applications tech-nologiques, peut aussi s'avérer problématique dans certains processus industriels. Longtemps resté une énigme, le rhéo-épaississement est désormais décrit de façon cohérente par le modèle de transition frictionnelle. Cet article présente ce modèle ainsi que les études numériques et expérimentales qui le valident. Sont ensuite abordées différentes perspectives d'applications offertes par la compréhension de ce phénomène. Résumé Shear-thickening is observed in dense particulate suspensions and consists in a severe increase of the suspension viscosity above an onset stress. This behavior, which is very useful for certain technological applications, can also be an issue in some industrial processes. Shear thickening was considered a puzzle for a long time. It can now be explained as a frictio-nal transition thanks to a recent theoretical model. This paper presents this model and its numerical and experimental validations. Different applications which may emerge from the understanding of this phenomenon are then discussed

Implication of cysteine residues in the selection of oxorhenium inhibitors of cyclophilin hCyp18

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Revealing the frictional transition in shear thickening suspensions - Data

Data corresponding to the article: Revealing the frictional transition in shear thickening suspension