Effect of Chain Stiffness on the Structure of Single-Chain Polymer Nanoparticles

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by purely intramolecular cross-linking of single polymer chains. By means of computer simulations, we investigate the conformational properties of SCNPs as a function of the bending stiffness of their linear polymer precursors. We investigate a broad range of characteristic ratios from the fully flexible case to those typical of bulky synthetic polymers. Increasing stiffness hinders bonding of groups separated by short contour distances and increases looping over longer distances, leading to more compact nanoparticles with a structure of highly interconnected loops. This feature is reflected in a crossover in the scaling behaviour of several structural observables. The scaling exponents change from those characteristic for Gaussian chains or rings in $\theta$-solvents in the fully flexible limit, to values resembling fractal or `crumpled' globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs.Comment: 20 pages, 17 figure

Reputation drives cooperative behaviour and network formation in human groups

Cooperativeness is a defining feature of human nature. Theoreticians have suggested several mechanisms to explain this ubiquitous phenomenon, including reciprocity, reputation, and punishment, but the problem is still unsolved. Here we show, through experiments conducted with groups of people playing an iterated Prisoner's Dilemma on a dynamic network, that it is reputation what really fosters cooperation. While this mechanism has already been observed in unstructured populations, we find that it acts equally when interactions are given by a network that players can reconfigure dynamically. Furthermore, our observations reveal that memory also drives the network formation process, and cooperators assort more, with longer link lifetimes, the longer the past actions record. Our analysis demonstrates, for the first time, that reputation can be very well quantified as a weighted mean of the fractions of past cooperative acts and the last action performed. This finding has potential applications in collaborative systems and e-commerce.This work was supported in part by MINECO (Spain) through grants PRODIEVO, FIS2011-25167, and FIS2009-09689, by Comunidad de Madrid (Spain) through grant MODELICO-CM, by Comunidad de Aragón (Spain) through a grant to the group FENOL, and by the EU FET Proactive project MULTIPLEX (contract no. 317532)

In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

CD44 promotes metastasis, chemoresistance, and stemness in different types of cancer and is a target for the development of new anti-cancer therapies. All CD44 isoforms share a common N-terminal domain that binds to hyaluronic acid (HA). Herein, we used a computational approach to design new potential CD44 antagonists and evaluate their target-binding ability. By analyzing 30 crystal structures of the HA-binding domain (CD44HAbd), we characterized a subdomain that binds to 1,2,3,4-tetrahydroisoquinoline (THQ)-containing compounds and is adjacent to residues essential for HA interaction. By computational combinatorial chemistry (CCC), we designed 168,190 molecules and compared their conformers to a pharmacophore containing the key features of the crystallographic THQ binding mode. Approximately 0.01% of the compounds matched the pharmacophore and were analyzed by computational docking and molecular dynamics (MD). We identified two compounds, Can125 and Can159, that bound to human CD44HAbd (hCD44HAbd) in explicit-solvent MD simulations and therefore may elicit CD44 blockage. These compounds can be easily synthesized by multicomponent reactions for activity testing and their binding mode, reported here, could be helpful in the design of more potent CD44 antagonists

Stability of Neural Firing in the Trigeminal Nuclei under Mechanical Whisker Stimulation

Sensory information handling is an essentially nonstationary process even under a periodic stimulation. We show how the time evolution of ridges in the wavelet spectrum of spike trains can be used for quantification of the dynamical stability of the neuronal responses to a stimulus. We employ this method to study neuronal responses in trigeminal nuclei of the rat provoked by tactile whisker stimulation. Neurons from principalis (Pr5) and interpolaris (Sp5i) show the maximal stability at the intermediate (50 ms) stimulus duration, whereas Sp5o cells “prefer” shorter (10 ms) stimulation. We also show that neurons in all three nuclei can perform as stimulus frequency filters. The response stability of about 33% of cells exhibits low-pass frequency dynamics. About 57% of cells have band-pass dynamics with the optimal frequency at 5 Hz for Pr5 and Sp5i, and 4 Hz for Sp5o, and the remaining 10% show no prominent dependence on the stimulus frequency. This suggests that the neural coding scheme in trigeminal nuclei is not fixed, but instead it adapts to the stimulus characteristics

Atomic motions in the αβ\alpha\beta-region of glass-forming polymers: Molecular versus Mode Coupling Theory approach

We present fully atomistic Molecular Dynamics simulation results on a main-chain polymer, 1,4-Polybutadiene, in the merging region of the $\alpha$- and $beta$-relaxations. A real space analysis reveals the occurrence of localized motions (``$\beta$-like'') in addition to the diffusive structural relaxation. A molecular approach provides a direct connection between the local conformational changes reflected in the atomic motions and the secondary relaxations in this polymer. Such local processes occur just in the time window where the $\beta$-process of the Mode Coupling Theory is expected. We show that the application of this theory is still possible, and yields an unusually large value of the exponent parameter. This result might originate from the competition between two mechanisms for dynamic arrest: intermolecular packing and intramolecular barriers for local conformational changes (``$\beta$-like'').Comment: 10 pages, 6 figure

Functional ingredients from Brassicaceae species: overview and perspectives

Brassicaceae vegetables are important crops consumed worldwide due to their unique flavor, and for their broadly recognized functional properties, which are directly related to their phytochemical composition. Isothiocyanates (ITC) are the most characteristic compounds, considered responsible for their pungent taste. Besides ITC, these vegetables are also rich in carotenoids, phenolics, minerals, and vitamins. Consequently, Brassica’s phytochemical profile makes them an ideal natural source for improving the nutritional quality of manufactured foods. In this sense, the inclusion of functional ingredients into food matrices are of growing interest. In the present work, Brassicaceae ingredients, functionality, and future perspectives are reviewed.Fil: Ramirez, Daniela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Abellán Victorio, Angel. Consejo Superior de Investigaciones Científicas; EspañaFil: Beretta, Hebe Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Camargo, Alejandra Beatriz. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias Enológicas y Agroalimentarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Moreno, Diego A.. Consejo Superior de Investigaciones Científicas; Españ

The Glycerol-Dependent Metabolic Persistence of Pseudomonas putida KT2440 Reflects the Regulatory Logic of the GlpR Repressor

The growth of the soil bacterium Pseudomonas putida KT2440 on glycerol as the sole carbon source is characterized by a prolonged lag phase, not observed with other carbon substrates. We examined the bacterial growth in glycerol cultures while monitoring the metabolic activity of individual cells. Fluorescence microscopy and flow cytometry, as well as the analysis of the temporal start of growth in single-cell cultures, revealed that adoption of a glycerol-metabolizing regime was not the result of a gradual change in the whole population but rather reflected a time-dependent bimodal switch between metabolically inactive (i.e., nongrowing) and fully active (i.e., growing) bacteria. A transcriptional Φ(glpD-gfp) fusion (a proxy of the glycerol-3-phosphate [G3P] dehydrogenase activity) linked the macroscopic phenotype to the expression of the glp genes. Either deleting glpR (encoding the G3P-responsive transcriptional repressor that controls the expression of the glpFKRD gene cluster) or altering G3P formation (by overexpressing glpK, encoding glycerol kinase) abolished the bimodal glpD expression. These manipulations eliminated the stochastic growth start by shortening the otherwise long lag phase. Provision of glpR in trans restored the phenotypes lost in the ΔglpR mutant. The prolonged nongrowth regime of P. putida on glycerol could thus be traced to the regulatory device controlling the transcription of the glp genes. Since the physiological agonist of GlpR is G3P, the arrangement of metabolic and regulatory components at this checkpoint merges a positive feedback loop with a nonlinear transcriptional response, a layout fostering the observed time-dependent shift between two alternative physiological states

Heterogeneous networks do not promote cooperation when humans play a Prisoner's dilemma

It is not fully understood why we cooperate with strangers on a daily basis. In an increasingly global world, where interaction networks and relationships between individuals are becoming more complex, different hypotheses have been put forward to explain the foundations of human cooperation on a large scale and to account for the true motivations that are behind this phenomenon. In this context, population structure has been suggested to foster cooperation in social dilemmas, but theoretical studies of this mechanism have yielded contradictory results so far; additionally, the issue lacks a proper experimental test in large systems. We have performed the largest experiments to date with humans playing a spatial Prisoner's Dilemma on a lattice and a scale-free network (1,229 subjects). We observed that the level of cooperation reached in both networks is the same, comparable with the level of cooperation of smaller networks or unstructured populations. We have also found that subjects respond to the cooperation that they observe in a reciprocal manner, being more likely to cooperate if, in the previous round, many of their neighbors and themselves did so, which implies that humans do not consider neighbors' payoffs when making their decisions in this dilemma but only their actions. Our results, which are in agreement with recent theoretical predictions based on this behavioral rule, suggest that population structure has little relevance as a cooperation promoter or inhibitor among humans.Work supported by Fundación Ibercivis and projects MOSAICO, PRODIEVO, FIS2008-01240, FIS2009-13364-C02-01, FIS2009-12648-C03-02, and Complexity-NET RESINEE, from Ministerio de Ciencia e Innovación (Spain); by project MODELICO-CM from Comunidad de Madrid (Spain); and by a project to FENOL from Comunidad de Aragón (Spain)

Dynamics in binary cluster crystals

As a result of the application of coarse-graining procedures to describe complex fluids, the study of systems consisting of particles interacting through bounded, repulsive pair potentials has become of increasing interest in the last years. A well known example is the so-called Generalized Exponential Model (GEM-$m$), for which the interaction between particles is described by the potential $v(r)=\epsilon\exp[-(r/\sigma)^m]$. Interactions with $m > 2$ lead to the formation of a novel phase of soft matter consisting of cluster crystals. Recent studies on the phase behavior of binary mixtures of GEM-$m$ particles have provided evidence for the formation of novel kinds of alloys, depending on the cross interactions between the two species. This work aims to study the dynamic behavior of such binary mixtures by means of extensive molecular dynamics simulations, and in particular to investigate the effect of the addition of non-clustering particles on the dynamic scenario of one-component cluster crystals. Analogies and differences with the one-component case are revealed and discussed by analyzing self- and collective dynamic correlators.Comment: 17 pages, 8 figures, submitted to JSTA