Hydration effects turn a highly stretched polymer from an entropic into an energetic spring

Polyethylene glycol (PEG) is a structurally simple and nontoxic water-soluble polymer that is widely used in medical and pharmaceutical applications as molecular linker and spacer. In such applications, PEG’s elastic response against conformational deformations is key to its function. According to text-book knowledge, a polymer reacts to the stretching of its end-to-end separation by a decrease in entropy that is due to the reduction of available conformations, which is why polymers are commonly called entropic springs. By a combination of single-molecule force spectroscopy experiments with molecular dynamics simulations in explicit water, we show that entropic hydration effects almost exactly compensate the chain conformational entropy loss at high stretching. Our simulations reveal that this entropic compensation is due to the stretching-induced release of water molecules that in the relaxed state form double hydrogen bonds with PEG. As a consequence, the stretching response of PEG is predominantly of energetic, not of entropic, origin at high forces and caused by hydration effects, while PEG backbone deformations only play a minor role. These findings demonstrate the importance of hydration for the mechanics of macromolecules and constitute a case example that sheds light on the antagonistic interplay of conformational and hydration degrees of freedom

Flat ring epimorphisms and universal localizations of commutative rings

We study different types of localizations of a commutative noetherian ring. More precisely, we provide criteria to decide: (a) if a given flat ring epimorphism is a universal localization in the sense of Cohn and Schofield; and (b) when such universal localizations are classical rings of fractions. In order to find such criteria, we use the theory of support and we analyse the specialization closed subset associated to a flat ring epimorphism. In case the underlying ring is locally factorial or of Krull dimension one, we show that all flat ring epimorphisms are universal localizations. Moreover, it turns out that an answer to the question of when universal localizations are classical depends on the structure of the Picard group. We furthermore discuss the case of normal rings, for which the divisor class group plays an essential role to decide if a given flat ring epimorphism is a universal localization. Finally, we explore several (counter)examples which highlight the necessity of our assumptions

The effect of temperature on single-polypeptide adsorption

The hydrophobic attraction (HA) is believed to be one of the main driving forces for protein folding. Understanding its temperature dependence promises a deeper understanding of protein folding. Herein, we present an approach to investigate the HA with a combined experimental and simulation approach, which is complementary to previous studies on the temperature dependence of the solvation of small hydrophobic spherical particles. We determine the temperature dependence of the free-energy change and detachment length upon desorption of single polypeptides from hydrophobic substrates in aqueous environment. Both the atomic force microscopy (AFM) based experiments and the molecular dynamics (MD) simulations show only a weak dependence of the free energy change on temperature. In fact, depending on the substrate, we find a maximum or a minimum in the temperature-dependent free energy change, meaning that the entropy increases or decreases with temperature for different substrates. These observations are in contrast to the solvation of small hydrophobic particles and can be rationalized by a compensation mechanism between the various contributions to the desorption force. On the one hand this is reminiscent of the protein folding process, where large entropic and enthalpic contributions compensate each other to result in a small free energy difference between the folded and unfolded state. On the other hand, the protein folding process shows much stronger temperature dependence, pointing to a fundamental difference between protein folding and adsorption. Nevertheless such temperature dependent single molecule desorption studies open large possibilities to study equilibrium and non-equilibrium processes dominated by the hydrophobic attraction

ZrCl4-catalyzed C-O bond to C-N bond formation: synthesis of 1,2,3-triazoles and their biological evaluation

A simple and efficient protocol was developed for the synthesis of aryl azides directly from aryl carbinols using ZrCl4as a Lewis acid catalyst. The azides were converted to novel triazoles under click reaction conditions, which were evaluated for their antimicrobial activity against various strains

Cancer stem cells in melanoma

The identification of cancer stem cells in various malignancies led to the hypothesis that these cells have the exclusive ability of self-renewal, contribute to the plasticity of the tumours and may be the cause for ineffective cancer therapies. Several markers of melanoma stem cells have been described in recent studies including CD133, CD166, Nestin and BMI-1. Further studies are necessary to identify, better define and understand the origin and function of cancer stem cells. If confirmed that cancer stem cells play an important role in malignancy, therapeutic strategies may need to be redirected towards these cells to circumvent the failure of conventional therapies

Dendritic Spine Morphology Determines Membrane-Associated Protein Exchange between Dendritic Shafts and Spine Heads

The purpose of this study was to examine whether variability in the shape of dendritic spines affects protein movement within the plasma membrane. Using a combination of confocal microscopy and the fluorescence loss in photobleaching technique in living hippocampal CA1 pyramidal neurons expressing membrane-linked GFP, we observed a clear correlation between spine shape parameters and the diffusion and compartmentalization of membrane-associated proteins. The kinetics of membrane-linked GFP exchange between the dendritic shaft and the spine head compartment were slower in dendritic spines with long necks and/or large heads than in those with short necks and/or small heads. Furthermore, when the spine area was reduced by eliciting epileptiform activity, the kinetics of protein exchange between the spine compartments exhibited a concomitant decrease. As synaptic plasticity is considered to involve the dynamic flux by lateral diffusion of membrane-bound proteins into and out of the synapse, our data suggest that spine shape represents an important parameter in the susceptibility of synapses to undergo plastic chang

A framework for future CAM software dedicated to additive manufacturing by multi-axis deposition

International audienceDeposition processes, such as Wire & Arc Additive Manufacturing (WAAM), have important perspectives in industry, due to their capacity to produce large near-shape parts with high productivity. Beyond process-material issues, deposition path planning is one of the major challenges to allow a wide use of these processes using multi-axis machines or robots. Early CAM software solutions dedicated to multi-axis additive manufacturing have been already commercialised. However, few elementary deposition strategies are currently available. In this article, the possibilities of multi-axis deposition and the developments needed to improve deposition path generation are highlighted through the analysis of a hollow half-sphere as a case study. Deposition strategies are experimentally tested on two different robotised polymer deposition systems. Based on the comparison of the trials, the issues related to the portability of technology from a specific machine setup to a different one are discussed. Finally, a framework for future Computer-Aided Multi-Axis Additive Manufacturing (CAMAAM) software is proposed

Molecular characterization of signalling pathways in cancer stem cells

To avoid artefacts introduced by culturing cells for extended periods of time, it is crucial to use low-passage patient-derived tumour cells. The ability to enrich, isolate and assay sub-populations of cells that behave as cancer stem cells (CSCs) from these primary cell lines is essential before performing characterizations such as gene-expression profiling. We have isolated cells from glioblastomas which show characteristics of CSCs. Although glioblastomas contain only a relatively small amount of putative CSCs, these cells express many genes which seem to be worthy targets for future therapies

On the relationship between peptide adsorption resistance and surface contact angle: a combined experimental and simulation single-molecule study

The force-induced desorption of single peptide chains from mixed OH/CH3-terminated self-assembled monolayers is studied in closely matched molecular dynamics simulations and atomic force microscopy experiments with the goal to gain microscopic understanding of the transition between peptide adsorption and adsorption resistance as the surface contact angle is varied. In both simulations and experiments, the surfaces become adsorption resistant against hydrophilic as well as hydrophobic peptides when their contact angle decreases below θ ≈ 50°-60°, thus confirming the so-called Berg limit established in the context of protein and cell adsorption. Entropy/enthalpy decomposition of the simulation results reveals that the key discriminator between the adsorption of different residues on a hydrophobic monolayer is of entropic nature and thus is suggested to be linked to the hydrophobic effect. By pushing a polyalanine peptide onto a polar surface, simulations reveal that the peptide adsorption resistance is caused by the strongly bound water hydration layer and characterized by the simultaneous gain of both total entropy in the system and total number of hydrogen bonds between water, peptide, and surface. This mechanistic insight into peptide adsorption resistance might help to refine design principles for anti-fouling surfaces