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The melting temperature depression of linear polyethylene lozenge single crystals is thoroughly examined in mixtures with a series of homogeneous high molecular weight branched polyethylene models, with special emphasis on the effect of short chain branching on the compatibility. The results indicate that the melting temperature of the lamellar single crystals is influenced both by the branching content of the surrounding matrix and by the relative volume concentration of the two polymers in the mixture. The discussion of the results is conducted around the compatibility of polymeric species as a function of the short chain branching content, invoking experimental and computational work performed by other authors. The observed depression indicates that the homogeneous mixing of the two polymers at the melting point may occur whenever the branching content is lower than 6–7 every 100 carbon atoms, a result that is reconciled with computer simulations and other experimental approaches.

The AS-48 bacteriocin is a potent antimicrobial polypeptide with enhanced stability due to its circular sequence of peptidic bonds. The mechanism of biological action is still not well understood in spite of both the elucidation of the molecular structure some years ago and several experiments performed that yielded valuable information about the AS-48 bacterial membrane poration activity. In this work, we present a computational study at an atomistic scale to analyze the membrane disruption mechanism. The process is based on the two-stage model: (1) peptide binding to the bilayer surface and (2) membrane poration due to the surface tension exerted by the peptide. Indeed, the induced membrane tension mechanism is able to explain stable formation of pores leading to membrane disruption. The atomistic detail obtained from the simulations allows one to envisage the contribution of the different amino acids during the poration process. Clustering of cationic residues and hydrophobic interactions between peptide and lipids seem to be essential ingredients in the process. GLU amino acids have shown to enhance the membrane disrupting ability of the bacteriocin. TRP24-TRP24 interactions make also an important contribution in the initial stages of the poration mechanism. The detailed atomistic information obtained from the simulations can serve to better understand bacteriocin structural characteristics to design more potent antimicrobial therapies.

We have measured the electrophoretic mobility and diffusion coefficient of carboxylate-modified and sulfate-modified polystyrene latex particles in poly(ethylene oxide) aqueous solutions. Carboxylate-modified polystyrene particles have shown a bound polymeric layer as the surface net charge vanishes even at very low poly(ethylene oxide) concentration. The polymeric layer causes a lower electrophoretic mobility and slower Brownian diffusion than that corresponding to the bare particles. We show that the diffusion is the result of a significantly increased effective particle size 2rheff = 30 nm. This bound layer is not present in sulfate-modified polystyrene latex particles. The interaction between the carboxylate-modified particle surface and the macromolecules has been confirmed by means of atomistic computer simulations. The grafted acrylate copolymers, which come from the preparation procedure of the latex particles, confer more hydrophobic surface ready to interact with the polymer. The simulations suggest that the interaction is modulated not only by the nature of the acrylic acid monomer but also by the length of the grafted copolymer. Our results have important implications for particle selection in microrheology experiments.

Repositioning of remdesivir and tenofovir against COVID-19 has shown only partial evidence of improving clinical outcomes, in clinical trials and observational studies respectively. The rationale behind this inconsistent efficacy remains unknown. Here, we developed an ensemble docking approach for the active triphosphate forms of both antivirals with the SARS-CoV-2 polymerase and the RNA chain complex, under the hypothesis that clinical observation could rely on the specificities of the drug-target interaction. Our model framework allowed accurate reconstruction of the remdesivir ensemble, which presented the strongest binding affinity and pose stability close to the natural counterpart dATP. We further observed a set of features of the tenofovir complex that suggests functional yet suboptimal interaction, likely resulting in limited viral inhibition in the absence of high intracellular concentration at target tissues. Our findings provide rationale for the mixed effectiveness of tenofovir-based compounds against SARS-CoV-2 and underscore the relevance of the intracellular availability of the nucleotide analogues relative to viral tropism.

Double crystalline multi-block copolymers exhibit two well-defined melting temperatures associated with the two phases formed by their constituent blocks. The crystalline superstructure formed in these copolymers is complex and depends on the miscibility of both comonomers. In this work, an innovative series of double crystalline Poly(ethylene terephthalate)-mb-poly(oxyhexane) multiblock copolymers were prepared in one pot. Previously synthesized low molecular weight poly(oxyhexane) telechelic diol and poly(ethylene terephthalate) oligomers were reacted by transesterification using an organic catalyst (DBU:BA), in a solvent-free process. The copolymerization was demonstrated by 1H NMR and 13C NMR spectroscopies and the random distribution of poly(oxyhexane) chains was confirmed. We found that all compositions exhibited double crystallinity, but the crystallization of the copolymers was strongly affected by PET/poly(oxyhexane) composition. When PET content in the copolymer decreases, the crystallization and melting temperatures of the poly(oxyhexane) phase decrease as well as its crystallization rate. Poly(oxyhexane) content increases induce similar changes in the PET phase. PET and poly(oxyhexane) chain segments form a one-phase melt according to SAXS. When the material is cooled from the melt, the PET phase crystallizes first (at higher temperatures) forming superstructural (micron size spherulites) templates. Upon further cooling, the crystallization of poly(oxyhexane) lamellae occurs, within the interlamellar regions of PET spherulitic templates. Furthermore, during crystallization of the copolymer, the amorphous regions of both components undergo phase separation, as evidenced by the presence of two Tgs. PLOM/AFM studies were performed and demonstrated the presence of micro-spherulitic morphology in the whole composition range. Considering all results, including temperature-dependent synchrotron SAXS/WAXS, we demonstrate the ability of poly(oxyhexane) to crystal

Polyethylene terephthalate (PET) is a nonbiodegradable polymer whose hydrolytic degradation can take decades. Intensive research has been performed to accelerate its hydrolytic degradation without significantly affecting its properties. In this work, PET was combined with poly(lactic acid) (PLA), a well-known biodegradable polymer, and the effect of PLA content in the crystallization of the PET component has been investigated in detail. To make the process sustainable, PET was polymerized using monomers that can be derived from PET chemical recycling (dimethyl terephthalate) and using organocatalysis (metal-free catalysts). First, low-molecular-weight telechelic PLA was prepared from the organocatalyzed ring-opening polymerization (ROP) of l-lactide followed by step-growth copolymerization with PET oligomers. The random copolymerization was confirmed by Fourier transform infrared (FTIR) and H NMR. We found that PET-ran-PLA copolymers are able to crystallize up to 24 mol % of PLA. Wide-angle and small-angle X-ray scattering (WAXS and SAXS) demonstrated that PLA units interrupt the average crystallizable PET sequences, decreasing its lamellar thickness, melting point, and crystallinity. The temperature dependence of the crystallization rate remarkably switches from nucleation control to diffusion control, as the mol % of PLA approaches the maximum tolerable limit for crystallization. The copolymers exhibited a microspherulitic PET morphology that changed to axialitic at relatively high contents of PLA. Preliminary hydrolytic degradation experiments demonstrate the potential degradation character of the prepared copolymers. If we consider the degradability of the copolymers obtained together with the green synthetic route employed (using dimethyl terephthalate, a monomer that can be obtained from the chemical route for recycling PET), the copolymers produced represent a step toward revalorization of PET recycled monomers for the production of sustainable materials.

Double crystalline multiblock copolymers exhibit two well-defined melting temperatures associated with the two phases formed by their constituent blocks. The crystalline superstructure formed in these copolymers is complex and depends on the miscibility of both comonomers. In this work, an innovative series of double crystalline poly(ethylene terephthalate)-mb-poly(oxyhexane) multiblock copolymers were prepared in one pot. Previously synthesized low molecular weight poly(oxyhexane)telechelic diol and poly(ethylene terephthalate) (PET) oligomers were reacted by transesterification using an organic catalyst (1,8-diazabicyclo[5.4.0]undec-7-ene/benzoic acid), in a solvent-free process. The copolymerization was demonstrated by H NMR and C NMR spectroscopies, and the random distribution of poly(oxyhexane) chains was confirmed. We found that all compositions exhibited double crystallinity, but the crystallization of the copolymers was strongly affected by the PET/poly(oxyhexane) composition. When the PET content in the copolymer decreases, the crystallization and melting temperatures of the poly(oxyhexane) phase decrease as well as its crystallization rate. The poly(oxyhexane) content increases induce similar changes in the PET phase. PET and poly(oxyhexane) chain segments form a one-phase melt according to small-angle X-ray scattering (SAXS). When the material is cooled from the melt, the PET phase crystallizes first (at higher temperatures), forming superstructural (micrometer size spherulites) templates. Upon further cooling, the crystallization of poly(oxyhexane) lamellae occurs, within the interlamellar regions of PET spherulitic templates. Furthermore, during crystallization of the copolymer, the amorphous regions of both components undergo phase separation, as evidenced by the presence of two T's. Polarized light optical microscopy/atomic force microscopy studies were performed and demonstrated the presence of microspherulitic morphology in the whole composition ran

The combination of hydrodynamic and electrophoretic experiments and computer simulations is a powerful approach to study the interaction between proteins. In this work, we present hydrodynamic and electrophoretic experiments in an aqueous solution along with molecular dynamics and hydrodynamic modeling to monitor and compute biophysical properties of the interactions between the extracellular domain of the HER2 protein (eHER2) and the monoclonal antibody trastuzumab (TZM). The importance of this system relies on the fact that the overexpression of HER2 protein is related with the poor prognosis breast cancers (HER2++ positives), while the TZM is a monoclonal antibody for the treatment of this cancer. We have found and characterized two different complexes between the TZM and eHER2 proteins (1:1 and 1:2 TZM:eHER2 complexes). The conformational features of these complexes regulate their hydrodynamic and electrostatic properties. Thus, the results indicate a high degree of molecular flexibility in the systems that ultimately leads to higher values of the intrinsic viscosity, as well as lower values of diffusion coefficient than those expected for simple globular proteins. A highly asymmetric charge distribution is detected for the monovalent complex (1:1 complex), which has strong implications in correlations between the experimental electrophoretic mobility and the modeled net charge. In order to understand the dynamics of these systems and the role of the specific domains involved, it is essential to find biophysical correlations between dynamics, macroscopic transport and electrostatic properties. The results should be of general interest for researchers working in this area.

La nanoindentación instrumentada dinámica es una técnica muy valiosa para medir propiedades mecánicas de materiales a escala submicrométrica, que permite obtener un perfil en función de la penetración en la superficie del material. Además, la mayor ventaja que ofrece la nanoindentación es su capacidad para caracterizar pequeños volúmenes de muestras con gran resolución espacial. Dicha capacidad se ha aplicado en este trabajo para abordar el estudio del bandeado esferulítico de poli(3-hidroxibutirato-co-3-hidroxivalerato) (P3HB-co-3HV). La estructura asociada a esta morfología ha sido objeto de controversia durante décadas, y este debate se ha intensificado recientemente con la aparición de nuevas evidencias experimentales. El estudio mediante nanoindentación se ha complementado con medidas de microscopía de fuerzas atómicas (AFM), concluyéndose que las esferulitas están formadas por valles y crestas, tanto mecánicos como morfológicos. Los resultados apoyan un modelo de plegamiento regular y continuo de las laminillas desde el centro de las esferulitas hacia el exterior

This feature article reviews several aspects of computational approaches to polyethylene melt and solid state properties in relation to existing experimental results. Based on 40 years of experience in the field, we offer a personal view of how computer simulations are helping to understand the physics of polyethylene as a model polymer. The first issue discussed is the molten state of polyethylene, including static and dynamic properties and entanglement features along with their impacts on rheological behaviour. We then examine the glass transition, crystallization process and solid state structure, including the interlamellar region. This is followed by brief descriptions of the latest advances in simulating mechanical properties and of the various methodologies used to simulate the physics of polyethylene. Throughout the manuscript, references are made to our own work and also to studies by many other authors that have nicely contributed to developments in simulating the physics of polyethylene in close agreement with experimental results.

Background In a broad range of human carcinomas gene amplification leads to HER2 overexpression, which has been proposed to cause spontaneous dimerization and activation in the absence of ligand. This makes HER2 attractive as a therapeutic target. However, the HER2 homodimerization mechanism remains unexplored. It has been suggested that the “back-to-back” homodimer does not form in solution. Notwithstanding, very recently the crystal structure of the HER2 extracellular domain homodimer formed with a “back-to-head” interaction has been resolved. We intend to explore the existence of such interactions. Methods A combination of experiments, molecular dynamics and hydrodynamic modeling were used to monitor the transport properties of HER2 in solution. Results & conclusions We have detected the HER2 extracellular domain homodimer in solution. The results show a high degree of molecular flexibility, which ultimately leads to quite higher values of the intrinsic viscosity and lower values of diffusion coefficient than those corresponding to globular proteins. This flexibility obeys to the open conformation of the receptor and to the large fluctuations of the different domains. We also report that for obtaining the correct hydrodynamic constants from the modeling one must consider the glycosylation of the systems. General significance Conformational features of epidermal growth factor receptors regulate their hydrodynamic properties and control their activity. It is essential to understand the dynamics of these systems and the role of the specific domains involved. To find biophysical correlations between dynamics and macroscopic transport properties is of general interest for researches working in this area. This article is part of a Special Issue entitled “Biochemistry of Synthetic Biology - Recent Developments” Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.

PCL was blended with pristine multiwalled carbon nanotubes (MWCNT) and with a nanohybrid obtained from the same MWCNT but grafted with low molecular weight PCL, employing concentrations of 0.25 to 5 wt % of MWCNT and MWCNT-g-PCL. Excellent CNT dispersion was found in all samples leading to supernucleation of both nanofiller types. Nanohybrids with 1 wt % or less MWCNTs crystallize faster than nanocomposites (due to supernucleation), while the trend eventually reverses at higher nanotubes content (because of plasticization). Rheological results show that yield-like behavior develops in both nanocomposites, even for the minimum content of carbon nanotubes. In addition, the MWCNT-g-PCL family, when compared with the neat polymer, exhibits lower values of viscosity and modulus in oscillatory shear, and higher compliance in creep. These rheological differences are discussed in terms of the plasticization effect caused by the existence of low molecular weight free and grafted PCL chains in the nanohybrids. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1310–1325.

Faceted polymer single crystals obtained from solution have been examined for decades. Most of the studies have been performed with linear polyethylene. It is well known that solution-grown linear polyethylene single crystals may exhibit different and often complex morphologies and habits. However, the effect of molecular architecture (i.e., short chain branching) in the morphology of the single crystals remains practically unexplored. At the highest crystallization temperature investigated, the shape of the crystals is lozenge-like, but with curved and slightly truncated {1 1 0} faces. As the crystallization temperature decreases, strong changes in the width-to-length ratio and, consequently in the characteristic angles of the single crystal occur. Interestingly, the single crystals obtained at the lowest crystallization temperature explored exhibit a nearly square shape. This phenomenon has not yet been observed in linear high molecular weight polyethylene, for which the characteristic lozenge habit with straight {1 1 0} faces is retained as crystallization temperature decreases. The application of the Shcherbina and Ungar approach to fit the unusual shapes of the branched PE single crystals obtained in this work requires a strong decrease in the ratio of the rates of propagation to the right and to the left of the growth edge. This result is probably linked to different steric conditions of chain attachments into non-equivalent niches induced by the presence of branches. 2016 Elsevier Ltd. All rights reserved

The stabilization of human papillomavirus type 16 virus-like particles has been examined by means of different techniques including dynamic and static light scattering, transmission electron microscopy and electrophoretic mobility. All these techniques provide different and often complementary perspectives about the aggregation process and generation of stabilized virus-like particles after a period of time of 48 hours at a temperature of 298 K. Interestingly, static light scattering results point towards a clear colloidal instability in the initial systems, as suggested by a negative value of the second virial coefficient. This is likely related to small repulsive electrostatic interactions among the particles, and in agreement with relatively small absolute values of the electrophoretic mobility and, hence, of the net surface charges. At this initial stage the small repulsive interactions are not able to compensate binding interactions, which tend to aggregate the particles. As time proceeds, an increase of the size of the particles is accompanied by strong increases, in absolute values, of the electrophoretic mobility and net surface charge, suggesting enhanced repulsive electrostatic interactions and, consequently, a stabilized colloidal system. These results show that electrophoretic mobility is a useful methodology that can be applied to screen the stabilization factors for virus-like particles during vaccine development.

Extensive molecular dynamics simulations of the macromolecular conformation and the melt dynamics for model polymers of different molecular weights have been carried out. The selected models are hydrogenated polybutadienes with a 2% content of ethyl branches and linear polyethylene. It will be shown that the density and chain stiffness are clearly affected by both the molecular weight and the presence of ethyl branches. Furthermore, the results obtained from the simulations on the molecular size and, more remarkably, chain dynamics, perfectly match the neutron scattering experiments performed by Zamponi et al. in hydrogenated polybutadienes. We observe a clear chain contraction and a slow dynamics for the hydrogenated polybutadiene with respect to the linear chain of the same molecular length. Using the Likhtman¿McLeish definitions, the obtained values of the entanglement relaxation time (¿e) and the tube diameter (a) are found to be in agreement with the available experimental data (by rheology and neutron spin echo) as well as with those obtained by the simulations. Finally, a very good agreement of diffusion coefficients as a function of the molecular weight between simulations and experiments is observed. Therefore, there exists a clear difference between the results obtained for branched and linear polyethylene, accounting for a definitive effect of the short chain branching on the conformational properties and the melt dynamics of polyolefins. ©The Royal Society of Chemistry 2016

Nanoindentation provides clear evidence that spherulite banding can be associated with a continuous modulation of mechanical properties from the more compliant peaks to the stiffer valleys. The structural arrangement in polymer-banded spherulites has intrigued scientists for many decades, and the debate has been recently intensified with the advent of new experimental evidence. The present paper approaches this issue by exploring the local mechanical properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-ringed spherulites via nanoindentation and discussing the confidence of the results. It was found that storage modulus and hardness across the banding morphology can be described as a sequence of regular oscillations with a periodicity that exactly matches the one observed using optical and atomic force microscopy. Results are consistent with the model of regular twisting of the lamellae, with flat-on arrangement in the low regions and edge-on lamellae in the crests.