Exploring the loading capacity of generation six to eight dendronized polymers in aqueous solution

Aspects of size, structural (im)perfection, inner density, and guest loading capacity of dendronized polymers (DPs) of high generation g (6≤g≤8) in aqueous solution were studied using electron paramagnetic resonance (EPR) spectroscopy on amphiphilic, spin- labeled guest molecules. The presented results show that the interior of the charged DPs is strongly polar, especially in comparison to their lower generation analogues 1-4. This is a direct sign of large amounts of water penetrating the DP surface, which in return mirrors structural imperfections and much lower than theoretically achievable segmental densities of these high generation DPs. Images obtained with atomic force microscopy (AFM) reveal that the high g DPs show no aggregation and give further insights into structural (im)perfections. EPR- spectroscopic data further show that despite their structural imperfections, these DPs can bind and release large numbers of amphiphilic molecules. It can be concluded that attention should be paid to synthesis which needs to develop a protocol that avoids the relatively large amount of defects generated in the direct conversion of PG4 to PG6 which had to be employed here

Formation of Cytoplasmic Actin-Cofilin Rods is Triggered by Metabolic Stress and Changes in Cellular pH

Actin dynamics plays a crucial role in regulating essential cell functions and thereby is largely responsible to a considerable extent for cellular energy consumption. Certain pathological conditions in humans, like neurological disorders such as Alzheimer’s disease or amyotrophic lateral sclerosis (ALS) as well as variants of nemaline myopathy are associated with cytoskeletal abnormalities, so-called actin-cofilin rods. Actin-cofilin rods are aggregates consisting mainly of actin and cofilin, which are formed as a result of cellular stress and thereby help to ensure the survival of cells under unfavorable conditions. We have used Dictyostelium discoideum, an established model system for cytoskeletal research to study formation and principles of cytoplasmic actin rod assembly in response to energy depletion. Experimentally, depletion of ATP was provoked by addition of either sodium azide, dinitrophenol, or 2-deoxy-glucose, and the formation of rod assembly was recorded by live-cell imaging. Furthermore, we show that hyperosmotic shock induces actin-cofilin rods, and that a drop in the intracellular pH accompanies this condition. Our data reveal that acidification of the cytoplasm can induce the formation of actin-cofilin rods to varying degrees and suggest that a local reduction in cellular pH may be a cause for the formation of cytoplasmic rods. We hypothesize that local phase separation mechanistically triggers the assembly of actin-cofilin rods and thereby influences the material properties of actin structures

Rates of Chemical Reactions Embedded in a Metabolic Network by Dissolution Dynamic Nuclear Polarisation NMR

International audienceThe isomerisation of 6-phosphogluconolactones and their hydrolyses into 6-phosphogluconic acid form a non enzymatic side cycle of the pentose-phosphate pathway (PPP) in cells. We show that dissolution dynamic nuclear polarization can be used for determining the kinetic rates of the involved transformations in real time. It is found that the hydrolysis of both lactones is significantly slower than the isomeration process, thereby shedding new light onto this subtle chemical process

NMR for food profiling - Long Drink, Short Experiment. An interdisciplinary approach to promoting judgement

Der vorliegende Beitrag stellt ein interdisziplinäres Projekt der Unterrichtsfächer Chemie und Ernährungs- und Verbraucher*innenbildung vor. Es zielt darauf ab, dass Schülerinnen und Schüler eine wissensbasierte Urteilskompetenz entwickeln, um in ihrem Alltag reflektierte Entscheidungen für eine nachhaltige Lebensführung zu treffen. Mit Hilfe dieser Urteilskompetenz können sie ein faktenbasiert begründetes Maß zwischen Konsum und Verzicht finden. (DIPF/Orig.)This article presents an interdisciplinary project of the subjects chemistry and nutrition and consumer education. It aims to develop a knowledge-based judgement competence for decisions for a sustainable lifestyle in everyday life. With this judgement competence, students can find a fact-based, well-founded measure between consumption and renunciation. (DIPF/Orig.

Identification of the allosteric binding site for thiazolopyrimidine on the C-type lectin langerin

Langerin is a mammalian C-type lectin expressed on Langerhans cells in the skin. As an innate immune cell receptor, Langerin is involved in coordinating innate and adaptive immune responses against various incoming threats. We have previously reported a series of thiazolopyrimidines as murine Langerin ligands. Prompted by the observation that its human homologue exhibits different binding specificities for these small molecules, we report here our investigations to define their exact binding site. By using structural comparison and molecular dynamics simulations, we showed that the nonconserved short loops have a high degree of conformational flexibility between the human and murine homologues. Sequence analysis and mutational studies indicated that a pair of residues are essential for the recognition of the thiazolopyrimidines. Taking solvent paramagnetic relaxation enhancement NMR studies together with a series of peptides occupying the same site, we could define the cleft between the short and long loops as the allosteric binding site for these aromatic heterocycles

Biphasic NMR of Hyperpolarized Suspensions─Real-Time Monitoring of Solute-to-Solid Conversion to Watch Materials Grow

Nuclear magnetic resonance (NMR) spectroscopy is a key method for the determination of molecular structures. Due to its intrinsically high (i.e., atomistic) resolution and versatility, it has found numerous applications for investigating gases, liquids, and solids. However, liquid-state NMR has found little application for suspensions of solid particles as the resonances of such systems are excessively broadened, typically beyond the detection threshold. Herein, we propose a route to overcoming this critical limitation by enhancing the signals of particle suspensions by >3.000-fold using dissolution dynamic nuclear polarization (d-DNP) coupled with rapid solid precipitation. For the proof-of-concept series of experiments, we employed calcium phosphate (CaP) as a model system. By d-DNP, we boosted the signals of phosphate $^{31}$P spins before rapid CaP precipitation inside the NMR spectrometer, leading to the inclusion of the hyperpolarized phosphate into CaP-nucleated solid particles within milliseconds. With our approach, within only 1 s of acquisition time, we obtained spectra of biphasic systems, i.e., micrometer-sized dilute solid CaP particles coexisting with their solution-state precursors. Thus, this work is a step toward real-time characterization of the solid–solution equilibrium. Finally, integrating the hyperpolarized data with molecular dynamics simulations and electron microscopy enabled us to shed light on the CaP formation mechanism in atomistic detail