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The COVID-19 pandemic has rekindled interest in the molecular mechanisms involved in the early steps of infection of cells by viruses. Compared to SARS-CoV-1 which only caused a relatively small albeit deadly outbreak, SARS-CoV-2 has led to fulminant spread and a full-scale pandemic characterized by efficient virus transmission worldwide within a very short time. Moreover, the mutations the virus acquired over the many months of virus transmission, particularly those seen in the Omicron variant, have turned out to result in an even more transmissible virus. Here, we focus on the early events of virus infection of cells. We review evidence that the first decisive step in this process is the electrostatic interaction of the spike protein with heparan sulfate chains present on the surface of target cells: Patches of cationic amino acids located on the surface of the spike protein can interact intimately with the negatively charged heparan sulfate chains, which results in the binding of the virion to the cell surface. In a second step, the specific interaction of the receptor binding domain (RBD) within the spike with the angiotensin-converting enzyme 2 (ACE2) receptor leads to the uptake of bound virions into the cell. We show that these events can be expressed as a semi-quantitative model by calculating the surface potential of different spike proteins using the Adaptive Poison-Boltzmann-Solver (APBS). This software allows visualization of the positive surface potential caused by the cationic patches, which increased markedly from the original Wuhan strain of SARS-CoV-2 to the Omicron variant. The surface potential thus enhanced leads to a much stronger binding of the Omicron variant as compared to the original wild-type virus. At the same time, data taken from the literature demonstrate that the interaction of the RBD of the spike protein with the ACE2 receptor remains constant within the limits of error. Finally, we briefly digress to other viruses and show the usefulness of these electrostatic processes and calculations for cell-virus interactions more generally., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lauster, Osterrieder, Haag, Ballauff and Herrmann.)

The effective charge of highly charged polyelectrolytes is significantly lowered by a condensation of counterions. This effect is more pronounced for divalent ions. Here we present a study of the counterion condensation to dendritic polyglycerol sulfate (dPGS) that consists of a hydrophilic dendritic scaffold onto which sulfate groups are appended. The interactions between the dPGS and divalent ions (Mg 2+ and Ca 2+ ) were analyzed using isothermal titration calorimetry (ITC) and showed no ion specificity upon binding, but clear competition between the monovalent and divalent ions. Our findings, in line with the latest theoretical studies, demonstrate that a large fraction of the monovalent ions is sequentially replaced with the divalent ions.

Insufficient stability of micellar drug delivery systems is still the major limitation to their systematic application in chemotherapy. This work demonstrates novel π-electron stabilized polyelectrolyte block copolymer micelles based on dendritic polyglycerolsulfate-cystamine- block -poly(4-benzoyl-1,4-oxazepan-7-one)-pyrene (dPGS-SS-POxPPh-Py) presenting a very low critical micelle concentration (CMC) of 0.3 mg L -1 (18 nM), 55-fold lower than that of conventional amphiphilic block copolymer micelles. The drug loading capacities of up to 13 wt% allow the efficient encapsulation of the chemotherapeutic Docetaxel (DTX). The spherical morphology of the micelles was proven by cryogenic electron microscopy (cryo-EM). Gaussian Analysis revealed well-defined sizes of 57 nm and 80 nm in the unloaded/loaded state, respectively. Experiments by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), fluorescence spectroscopy, and cross-polarization solid-state 13 C NMR studied the π-π interactions between the core-forming block segment of dPGS-SS-POxPPh-Py and DTX. The findings point to a substantial contribution of these noncovalent interactions to the system's high stability. By confocal laser scanning microscopy (CLSM), the cellular uptake of fluorescein-labelled FITC-dPGS-SS-POxPPh-Py micelles was monitored after one day displaying the successful cell insertion of the cargo-loaded systems. To ensure the drug release in cancerous cells, the disassembly of the micellar DTX-formulations was achieved by reductive and enzymatic degradation studied by light scattering and GPC experiments. Further, no size increase nor disassembly in the presence of human serum proteins after four days was detected. The precise in vitro drug release was also given by the high potency of inhibiting cancer cell growth, finding half-maximal inhibitory concentrations (IC 50 ) efficiently reduced to 68 nM coming along with high viabilities of the empty polymer materials tested on tumor-derived HeLa, A549, and McF-7 cell lines after two days. This study highlights the substantial potential of micelles tailored through the combination of π-electron stabilization with dendritic polyglycerolsulfate for targeted drug delivery systems, enabling them to have a significant foothold in the clinical treatment of cancer.

We present a model describing the binding of biological signaling proteins to highly charged polymer networks. The networks are formed by polyelectrolyte chains for which the distance between two charges at the chain is smaller than the Bjerrum length. Counterion condensation on such highly charged chains immobilizes a part of the counterions which do no more contribute to the osmotic pressure. The Donnan-equilibrium between the polymer network and the aqueous solution with salt concentration c s b is used to calculate the salt concentration of the co- and counterions c s g entering the network. Two factors lead to adsorption of proteins to charged polymer networks: i) The electrostatic interaction between the network and the protein is given by the Donnan-potential of the network and the net charge of the protein. In addition to this leading term, a second term describes the change of the Born-energy of the proteins when entering the network. ii) The interaction of the protein with the highly charged chains within the network is governed by counterion release: Patches of positive charge at the protein become multivalent counterions of the polyelectrolyte chains thus releasing a concomitant number of condensed counterions. The model is compared to experimental data obtained on a set of biohybrid polymer networks composed of crosslinked glycosaminoglycan chains that interact with a mixture of key signaling proteins. The analysis of the experimental binding constants reveals that the counterion release mechanism is decisive for protein adsorption to the network at physiological salt concentration. We present a model describing the binding of biological signaling proteins to highly charged polymer networks. The model is compared to experimental data obtained on a set of biohybrid polymer networks composed of crosslinked glycosaminoglycan chains that interact signaling proteins. Factors leading to protein binding to networks can be discussed on the basis of this model. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

The objective of this study was to establish if polyglycerols with sulfate or sialic acid functional groups interact with high mobility group box 1 (HMGB1), and if so, which polyglycerol could prevent loss of morphological plasticity in excitatory neurons in the hippocampus. Considering that HMGB1 binds to heparan sulfate and that heparan sulfate has structural similarities with dendritic polyglycerol sulfates (dPGS), we performed the experiments to show if polyglycerols can mimic heparin functions by addressing the following questions: (1) do dendritic and linear polyglycerols interact with the alarmin molecule HMGB1? (2) Does dPGS interaction with HMGB1 influence the redox status of HMGB1? (3) Can dPGS prevent the loss of dendritic spines in organotypic cultures challenged with lipopolysaccharide (LPS)? LPS plays a critical role in infections with Gram-negative bacteria and is commonly used to test candidate therapeutic agents for inflammation and endotoxemia. Pathologically high LPS concentrations and other stressful stimuli cause HMGB1 release and post-translational modifications. We hypothesized that (i) electrostatic interactions of hyperbranched and linear polysulfated polyglycerols with HMGB1 will likely involve sites similar to those of heparan sulfate. (ii) dPGS can normalize HMGB1 compartmentalization in microglia exposed to LPS and prevent dendritic spine loss in the excitatory hippocampal neurons. We performed immunocytochemistry and biochemical analyses combined with confocal microscopy to determine cellular and extracellular locations of HMGB1 and morphological plasticity. Our results suggest that dPGS interacts with HMGB1 similarly to heparan sulfate. Hyperbranched dPGS and linear sulfated polymers prevent dendritic spine loss in hippocampal excitatory neurons. MS/MS analyses reveal that dPGS-HMGB1 interactions result in fully oxidized HMGB1 at critical cysteine residues (Cys23, Cys45, and Cys106). Triply oxidized HMGB1 leads to the loss of its pro-inflammatory action and could participate in dPGS-mediated spine loss prevention. LPG-Sia exposure to HMGB1 results in the oxidation of Cys23 and Cys106 but does not normalize spine density.

We present a thermodynamic investigation of the interaction of heparin with lysozyme in the presence of potassium glutamate (KGlu). The binding constant K b is measured by isothermal titration calorimetry (ITC) in a temperature range from 288 to 310 K for concentrations of KGlu between 25 and 175 mM. The free energy of binding Δ G b derived from K b is strongly decreasing with increasing concentration of KGlu, whereas the dependence of Δ G b on temperature T is found to be small. The decrease of Δ G b can be explained in terms of counterion release: Binding of lysozyme to the strong polyelectrolyte heparin liberates approximately three of the condensed counterions of heparin, thus increasing the entropy of the system. The dependence of Δ G b on T , on the other hand, is traced back to a change of hydration of the protein and the polyelectrolyte upon complex formation. This dependence is quantitatively described by the parameter Δ w that depends on T and vanishes at a characteristic temperature T 0 . A comparison of the complex formation in the presence of KGlu with the one in the presence of NaCl demonstrates that the parameters related to hydration are changed considerably. The characteristic temperature T 0 in the presence of KGlu solutions is considerably smaller than that in the presence of NaCl solutions. The change of specific heat Δ c p is found to become more negative with increasing salt concentration: This finding agrees with the model-free analysis by the generalized van't Hoff equation. The entire analysis reveals a small but important change of the free energy of binding by hydration. It shows that these ion-specific Hofmeister effects can be modeled quantitatively in terms of a characteristic temperature T 0 and a parameter describing the dependence of Δ c p on salt concentration.

The unfolding transition of proteins in aqueous solution containing various salts or uncharged solutes is a classical subject of biophysics. In many cases, this transition is a well-defined two-stage equilibrium process which can be described by a free energy of transition Δ G u and a transition temperature T m . For a long time, it has been known that solutes can change T m profoundly. Here we present a phenomenological model that describes the change of T m with the solute concentration c s in terms of two effects: (i) the change of the number of correlated counterions Δ n ci and (ii) the change of hydration expressed through the parameter Δ w and its dependence on temperature expressed through the parameter dΔ c p /d c s . Proteins always carry charges and Δ n ci describes the uptake or release of counterions during the transition. Likewise, the parameter Δ w measures the uptake or release of water during the transition. The transition takes place in a reservoir with a given salt concentration c s that defines also the activity of water. The parameter Δ n ci is a measure for the gain or loss of free energy because of the release or uptake of ions and is related to purely entropic effects that scale with ln  c s . Δ w describes the effect on Δ G u through the loss or uptake of water molecules and contains enthalpic as well as entropic effects that scale with c s . It is related to the enthalpy of transition Δ H u through a Maxwell relation: the dependence of Δ H u on c s is proportional to the dependence of Δ w on temperature. While ionic effects embodied in Δ n ci are independent of the kind of salt, the hydration effects described through Δ w are directly related to Hofmeister effects of the various salt ions. A comparison with literature data underscores the general validity of the model., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Evidence is strengthening to suggest that the novel SARS-CoV-2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although the mutations in the spike protein are known, the molecular basis for why the additional mutations in the spike protein that have not previously occurred account for Omicron's higher infection potential, is not understood. We propose, based on chemical rational and molecular dynamics simulations, that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs. wild type) increases binding to cellular polyanionic receptors, such as heparan sulfate due to multivalent charge-charge interactions. This observation is a starting point for targeted drug development., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

We present a thermodynamic study of the interaction of synthetic, linear polyelectrolytes with bovine serum albumin (BSA). All polyelectrolytes are based on poly(allyl glycidyl ether) which has been modified by polymer-analogous reaction with anionic (-SO 3 Na), cationic (-NH 3 Cl or -NHMe 2 Cl) or zwitterionic groups (-NMe 2 (CH 2 ) 3 SO 3 ). While the anionic polymer shows a very weak interaction, the zwitterionic polymer exhibits no interaction with BSA (pI = 4.7) under the applied pH = 7.4, ionic strength (I = 23-80 mM) and temperature conditions (T = 20-37 °C). A strong binding, however, was observed for the polycations bearing primary amino or tertiary dimethyl amino groups, which could be analysed in detail by isothermal titration calorimetry (ITC). The analysis was done using an expression which describes the free energy of binding, Δ G b , as the function of the two decisive variables, temperature, T , and salt concentration, c s . The underlying model splits Δ G b into a term related to counterion release and a term related to water release. While the number of released counter ions is similar for both systems, the release of bound water is more important for the primary amine compared to the tertiary N , N -dimethyl amine presenting polymer. This finding is further traced back to a closer contact of the polymers' protonated primary amino groups in the complex with oppositely charged moieties of BSA as compared to the bulkier protonated tertiary amine groups. We thus present an investigation that quantifies both driving forces for electrostatic binding, namely counterion release and change of hydration, which contribute to a deeper understanding with direct impact on future advancements in the biomedical field.

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC 50 of 67 μg mL -1 (approx. 1.6 μm). This synthetic polysulfate exhibits more than 60-fold higher virus inhibitory activity than heparin (IC 50 : 4084 μg mL -1 ), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interactions, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in light of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1 H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81-187 nm, strong negative charges between -52 and -41 mV, and low critical micelle concentrations (CMCs) of up to 1.13-3.58 mg/L (134-527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8-17 wt %). The release was selectively triggered by glutathione (GSH) and lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high cancer cell toxicity of Sunitinib-loaded micelles (IC 50 2.5 μg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS 7.8 -SS-PCL 7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG 3.9 -SS-PCL 7.8 . As a proof of concept, Sunitinib-loaded dPGS-SS-poly(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

The lithiation of crystalline silicon was studied over several cycles using operando neutron reflectometry over six cycles. A thin layer of aluminum oxide was employed as an artificial coating on the silicon to suppress the solid electrolyte interphase (SEI) layer-related aging effects. Initially, the artificial SEI prevented side effects but led to increased lithium trapping. This layer degraded after two cycles, followed by side reactions, which decrease the coulombic efficiency. No hint for electrode fracturization was found even though the lithiation depth exceeded 1 μm. Two distinct zones with high and low lithium concentrations were found, initially separated by a sharp interface, which broadens with cycling. The correlation of the reflectometry results with the electrochemical current showed the lithium fraction that is lithiated in the silicon and the lithium consumed in side reactions. Also, neutron reflectometry was used to quantify the amount of lithium that remained inside of the silicon. Additional electrochemical impedance spectroscopy was used to gain insights into the electrical properties of the sample via fitting to an equivalent circuit.

A theoretical model is presented for the free energy Δ G b of complex formation between a highly charged polyelectrolyte and a protein. The model introduced here comprises both the effect of released counterions and the uptake or release of water molecules during complex formation. The resulting expression for Δ G b is hence capable of describing the dependence of Δ G b on temperature as well as on the concentration of salt in the system: An increase of the salt concentration in the solution increases the activity of the ions and counterion release becomes less effective for binding. On the other hand, an increased salt concentration leads to the decrease of the activity of water in bulk. Hence, release of water molecules during complex formation will be more advantageous and lead to an increase of the magnitude of Δ G b and the binding constant. It is furthermore demonstrated that the release or uptake of water molecules is the origin of the marked enthalpy-entropy cancellation observed during complex formation of polyelectrolytes with proteins. The comparison with experimental data on complex formation between a synthetic (sulfated dendritic polyglycerol) and natural polyelectrolytes (DNA; heparin) with proteins shows full agreement with theory., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The counterions neutralizing the charges on polyelectrolytes such as DNA or heparin may dissociate in water and greatly influence the interaction of such polyelectrolytes with biomolecules, particularly proteins. In this Review we give an overview of studies on the interaction of proteins with polyelectrolytes and how this knowledge can be used for medical applications. Counterion release was identified as the main driving force for the binding of proteins to polyelectrolytes: Patches of positive charge become multivalent counterions of the polyelectrolyte and lead to the release of counterions from the polyelectrolyte and a concomitant increase in entropy. This is shown from investigations on the interaction of proteins with natural and synthetic polyelectrolytes. Special emphasis is paid to sulfated dendritic polyglycerols (dPGS). The Review demonstrates that we are moving to a better understanding of charge-charge interactions in systems of biological relevance. Research along these lines will aid and promote the design of synthetic polyelectrolytes for medical applications., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

We describe the preparation of a poly(acrylic acid) (PAA) brush, polymerized by atom transfer radical polymerization (ATRP) of tert -butyl acrylate ( t BA) and subsequent acid hydrolysis, on the flat gold surfaces of quartz-crystal microbalance (QCM) crystals. The PAA brushes were characterized by Fourier transform infrared (FT-IR) spectroscopy, ellipsometry and water contact angle analysis. The interaction of the PAA brushes with human serum albumin (HSA) was studied for a range of ionic strengths and pH conditions by quartz-crystal microbalance with dissipation monitoring (QCM-D). The quantitative analysis showed a strong adsorption of protein molecules onto the PAA brush. By increasing the ionic strength, we were able to release a fraction of the initially bound HSA molecules. This finding highlights the importance of counterions in the polyelectrolyte-mediated protein adsorption/desorption. A comparison with recent calorimetric studies related to the binding of HSA to polyelectrolytes allowed us to fully analyze the QCM data based on the results of the thermodynamic analysis of the binding process.

Glycosaminoglycan (GAG)-protein binding governs critically important signaling events in living matter. Aiming at a quantitative analysis of the involved processes, we herein present a thermodynamic study of the interaction of the model GAG heparin and lysozyme in aqueous solution. Heparin is a highly charged linear polyelectrolyte with a charge parameter of 2.9 (37 °C). The binding constant K b was determined by ITC as a function of the temperature and ionic strength adjusted through the concentration c was used to determine the net number of released counterions. Moreover, the binding constant at a reference salt concentration of 1 M s (1 M) was determined by extrapolation. The dependence on temperature of c s was used to determine the net number of released counterions. Moreover, the binding constant at a reference salt concentration of 1 M K b (1 M) was determined by extrapolation. The dependence on temperature of K b was used to dissect the binding free energy ΔG b into the respective enthalpies ΔH b and entropies ΔS b together with the specific heat Δc p . A strong enthalpy-entropy cancelation was found similar to the results for many other systems. The binding free energy Δ G b could furthermore be split up into a part Δ G ci due to counterion release and a residual part Δ G res . The latter quantity reflects specific contributions as, e.g., salt bridges, van der Waals interactions, or hydrogen bonds. The entire analysis shows that heparin-lysozyme interactions are mainly caused by counterion release; that is, ca. three counterions are being released upon binding one lysozyme molecule. Our reported approach of quantifying interactions between glycosaminoglycans and proteins is generally applicable and suitable to provide new insights in the physical modulation of biomolecular signals.

Experimental and kinetic modelling studies are presented to investigate the mechanism of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by hydrogen peroxide (H 2 O 2 ) catalyzed by peroxidase-like Pt nanoparticles immobilized in spherical polyelectrolyte brushes (SPB-Pt). Due to the high stability of SPB-Pt colloidal, this reaction can be monitored precisely in situ by UV/VIS spectroscopy. The time-dependent concentration of the blue-colored oxidation product of TMB expressed by different kinetic models was used to simulate the experimental data by a genetic fitting algorithm. After falsifying the models with abundant experimental data, it is found that both H 2 O 2 and TMB adsorb on the surface of Pt nanoparticles to react, indicating that the reaction follows the Langmuir-Hinshelwood mechanism. A true rate constant k, characterizing the rate-determining step of the reaction and which is independent on the amount of catalysts used, is obtained for the first time. Furthermore, it is found that the product adsorbes strongly on the surface of nanoparticles, thus inhibiting the reaction. The entire analysis provides a new perspective to study the catalytic mechanism and evaluate the catalytic activity of the peroxidase-like nanoparticles., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here, we use cryo soft X-ray tomography (cryo-SXT), which delivers 3D ultrastructural volumes of intact cells without chemical fixation or staining, to gain insight about nanoparticle uptake for nanomedicine. We initially used dendritic polyglycerol sulfate (dPGS) with potential diagnostic and therapeutic applications in inflammation. Although dPGS-coated gold nanoparticle (dPGS-AuNP) uptake followed a conventional endocytic/degradative pathway in human lung epithelial cell lines (A549), with cryo-SXT, we detected ∼5% of dPGS-AuNPs in the cytoplasm, a level undetectable by confocal light microscopy. We also observed ∼5% of dPGS-AuNPs in a rarely identified subcellular site, namely, lipid droplets, which are important for cellular energy metabolism. Finally, we also found substantial changes in the quantity of cytoplasmic organelles upon dPGS-AuNP uptake over the 1-6 h incubation period; the number of small vesicles and mitochondria significantly increased, and the number of multivesicular bodies and the number and volume of lipid droplets significantly decreased. Although nearly all organelle numbers at 6 h were still significantly different from controls, most appeared to be returning to normal levels. To test for generality, we also examined cells after uptake of gold nanoparticles coated with a different agent, polyethylenimine (PEI), used for nucleic acid delivery. PEI nanoparticles did not enter lipid droplets, but they induced similar, albeit less pronounced, changes in the quantity of cytoplasmic organelles. We confirmed these changes in organelle quantities for both nanoparticle coatings by confocal fluorescence microscopy. We suggest this cytoplasmic remodeling could reflect a more common cellular response to coated gold nanoparticle uptake.

A thermodynamic study of the adsorption of Human Serum Albumin (HSA) onto spherical polyelectrolyte brushes (SPBs) by isothermal titration calorimetry (ITC) is presented. The SPBs are composed of a solid polystyrene core bearing long chains of poly(acrylic acid). ITC measurements done at different temperatures and ionic strengths lead to a full set of thermodynamicbinding constants together with the enthalpies and entropies of binding. The adsorption of HSA onto SPBs is described with a two-step model. The free energy of binding ΔGb depends only weakly on temperature because of a marked compensation of enthalpy by entropy. Studies of the adsorbed HSA by Fourier transform infrared spectroscopy (FT-IR) demonstrate no significant disturbance in the secondary structure of the protein. The quantitative analysis demonstrates that counterion release is the major driving force for adsorption in a process where proteins become multivalent counterions of the polyelectrolyte chains upon adsorption. A comparison with the analysis of other sets of data related to the binding of HSA to polyelectrolytes demonstrates that the cancellation of enthalpy and entropy is a general phenomenon that always accompanies the binding of proteins to polyelectrolytes dominated by counterion release., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photothermal conversion (PTC) nanostructures have great potential for applications in many fields, and therefore, they have attracted tremendous attention. However, the construction of a PTC nanoreactor with multi-compartment structure to achieve the combination of unique chemical properties and structural feature is still challenging due to the synthetic difficulties. Herein, we designed and synthesized a catalytically active, PTC gold (Au)@polydopamine (PDA) nanoreactor driven by infrared irradiation using assembled PS-b-P2VP nanosphere as soft template. The particles exhibit multi-compartment structure which is revealed by 3D electron tomography characterization technique. They feature permeable shells with tunable shell thickness. Full kinetics for the reduction reaction of 4-nitrophenol has been investigated using these particles as nanoreactors and compared with other reported systems. Notably, a remarkable acceleration of the catalytic reaction upon near-infrared irradiation is demonstrated, which reveals for the first time the importance of the synergistic effect of photothermal conversion and complex inner structure to the kinetics of the catalytic reduction. The ease of synthesis and fresh insights into catalysis will promote a new platform for novel nanoreactor studies.

We present a comprehensive analysis of the energetics of the binding of lysozyme to dendritic polyglycerolsulfate (dPGS) in aqueous solution. This system is a perfect model for studying the interaction of proteins with polyelectrolytes. We discuss and model the free energy of binding Δ G b = - k B T ln K b as the function of the two decisive variables, namely, the salt concentration c s and the temperature T . The system lysozyme/dPGS exhibits a strong enthalpy-entropy compensation throughout the entire range of temperature, similar to the one observed for the interaction of DNA with various proteins. Following a suggestion of Dragan et al. [ Eur. Biophys. J. 2017 , 46 , 301], the free energy Δ G to 1 M salt concentration. Plots of dlog b can be split up into Δ G b = 1 M in order to obtain Δ G res + Δ G can be independently obtained by implicit solvent molecular dynamics simulations made up to salt concentrations of 1 M. Good agreement of the experiment and simulation within prescribed limits of error is found. Moreover, Δ ci , where Δ G ci denotes the part due to counterion release, whereas Δ G res is the part obtained by extrapolation of Δ G b to 1 M salt concentration. Plots of dlog K b /dlog c s lead to perfectly straight lines that can be extrapolated to c s = 1 M in order to obtain Δ G res . Both Δ G res and Δ G ci can be independently obtained by implicit solvent molecular dynamics simulations made up to salt concentrations of 1 M. Good agreement of the experiment and simulation within prescribed limits of error is found. Moreover, Δ G res is shown to be caused by direct unscreened electrostatic contacts or salt bridges between dPGS and lysozyme. Because Δ G ci = - T Δ S ci where Δ S ci is the entropy due to counterion release, the entire binding entropy Δ S b can be split up as Δ S b = Δ S ci + Δ S res . Plots of the binding enthalpy Δ H b versus Δ S res lead to a perfect master curve for the system dPGS/lysozyme. These findings suggest that the strong enthalpy-entropy cancellation found for this system is an entirely nonelectrostatic phenomenon solely due to solvation or desolvation by water. Thus, the results obtained here on the model system dPGS and lysozyme are in full agreement with the conclusion drawn by Dragan et al. for the binding of DNA to various proteins.

This study reports the use of operando small-angle neutron scattering to investigate processes in an operating Li/S battery. The combination with impedance spectroscopy yields valuable insights into the precipitation and dissolution of lithium sulfide during 10 cycles of galvanostatic cycling. The use of a deuterated electrolyte increases strongly the sensitivity to detect the sulfur and Li 2 S precipitates at the carbon host electrode and allows us to observe the time-dependent initial wetting of the system. No correlation of the scattering signal of the micropores with either lithium sulfide or sulfur is observable during the whole course of the experiment. Hence both reaction products do not precipitate inside the microporous structure but on the outer surface of the micrometer-sized carbon fibers used in this study. The excellent scattering contrast allows a detailed analysis of the formation and dissolution process of nanoscopic Li 2 S structures. While lithium sulfide particles grow homogeneously during the precipitation period, smaller Li 2 S particles dissolve first followed by a sudden dissolution of the larger Li 2 S particles.

We discuss recent investigations of the interaction of polyelectrolytes with proteins. In particular, we review our recent studies on the interaction of simple proteins such as human serum albumin (HSA) and lysozyme with linear polyelectrolytes, charged dendrimers, charged networks, and polyelectrolyte brushes. In all cases discussed here, we combined experimental work with molecular dynamics (MD) simulations and mean-field theories. In particular, isothermal titration calorimetry (ITC) has been employed to obtain the respective binding constants K b and the Gibbs free energy of binding. MD simulations with explicit counterions but implicit water demonstrate that counterion release is the main driving force for the binding of proteins to strongly charged polyelectrolytes: patches of positive charges located on the surface of the protein become multivalent counterions of the polyelectrolyte, thereby releasing a number of counterions condensed on the polyelectrolyte. The binding Gibbs free energy due to counterion release is predicted to scale with the logarithm of the salt concentration in the system, which is verified by both simulations and experiment. In several cases, namely, for the interaction of proteins with linear polyelectrolytes and highly charged hydrophilic dendrimers, the binding constant could be calculated from simulations to very good approximation. This finding demonstrated that in these cases explicit hydration effects do not contribute to the Gibbs free energy of binding. The Gibbs free energy can also be used to predict the kinetics of protein uptake by microgels for a given system by applying dynamic density functional theory. The entire discussion demonstrates that the direct comparison of theory with experiments can lead to a full understanding of the interaction of proteins with charged polymers. Possible implications for applications, such as drug design, are discussed.

MoS 2 , a typical layered transition-metal dichalcogenide, is promising as an electrode material in supercapacitors. However, its low electrical conductivity could lead to limited capacitance if applied in electrochemical devices. Herein, a new nanostructure composed of hollow carbon-MoS 2 -carbon was successfully synthesized through an l-cysteine-assisted hydrothermal method by using gibbsite as a template and polydopamine as a carbon precursor. After calcination and etching of the gibbsite template, uniform hollow platelets, which were made of a sandwich-like assembly of partial graphitic carbon and two-dimensional layered MoS 2 flakes, were obtained. The platelets showed excellent dispersibility and stability in water, and good electrical conductivity due to carbon provided by the calcination of polydopamine coatings. The hollow nanoplate morphology of the material provided a high specific surface area of 543 m 2  g -1 , a total pore volume of 0.677 cm 3  g -1 , and fairly small mesopores (≈5.3 nm). The material was applied in a symmetric supercapacitor and exhibited a specific capacitance of 248 F g -1 (0.12 F cm -2 ) at a constant current density of 0.1 A g -1 ; thus suggesting that hollow carbon-MoS 2 -carbon nanoplates are promising candidate materials for supercapacitors., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Metal nanoparticles are the most frequently used nanostructures in plasmonics. However, besides nanoparticles, metal nanowires feature several advantages for applications. Their elongation offers a larger interaction volume, their resonances can reach higher quality factors, and their mode structure provides better coupling into integrated hybrid dielectric-plasmonic circuits. It is crucial though, to control the distance of the wire to a supporting substrate, to another metal layer or to active materials with sub-nanometer precision. A dielectric coating can be utilized for distance control, but it must not degrade the plasmonic properties. In this paper, we introduce a controlled synthesis and coating approach for silver nanowires to fulfill these demands. We synthesize and characterize silver nanowires of around 70 nm in diameter. These nanowires are coated with nm-sized silica shells using a modified Stöber method to achieve a homogeneous and smooth surface quality. We use transmission electron microscopy, dark-field microscopy and electron-energy loss spectroscopy to study morphology and plasmonic resonances of individual nanowires and quantify the influence of the silica coating. Thorough numerical simulations support the experimental findings showing that the coating does not deteriorate the plasmonic properties and thus introduce silver nanowires as usable building blocks for integrated hybrid plasmonic systems.

We study the thermodynamics of the interaction between human serum albumin (HSA) and dendritic polyglycerol sulfate (dPGS) of different sizes (generations) by isothermal titration calorimetry (ITC) and computer simulations. The analysis by ITC revealed the formation of a 1:1 complex for the dPGS-G2 of second generation. The secondary structure of HSA remained unchanged in the presence of dPGS-G2, as shown by circular dichroism. For higher generations, several HSA are bound to one polymer (dPGS-G4: 2; dPGS-G5.5: 4). The Gibbs free energy Δ G b was determined at different temperatures and salt concentrations. The binding constant K b exhibited a logarithmic dependence on the salt concentration thus indicating a marked contribution of counterion-release entropy to Δ G b . The number of released counterions (∼4) was found to be independent of temperature. In addition, the temperature dependence of Δ G b was small, whereas the enthalpy Δ H ITC was found to vary strongly with temperature. The corresponding heat capacity change Δ C p,ITC for different generations was of similar values [8 kJ/(mol K)]. The nonlinear van't Hoff analysis of Δ G b revealed a significant heat capacity change Δ C p,vH of similar magnitude [6 kJ/(mol K)] accompanied by a strong enthalpy-entropy compensation. Δ G b obtained by molecular dynamics simulation with implicit water and explicit ions coincided with experimental results. The agreement indicates that the enthalpy-entropy compensation assigned to hydration effects is practically total and the binding affinity is fully governed by electrostatic interactions.

The interaction between dendritic polyglycerol sulfate (dPGS) of the second generation and lysozyme was studied by isothermal titration calorimetry (ITC) at different temperatures and salt concentrations. Analysis by ITC showed that 2-3 lysozyme molecules were bound to each dPGS. The resulting binding constant K b and the Gibbs free energy Δ G o decreased markedly with increasing salt concentration but were nearly independent of temperature. The salt dependence of K b led to the conclusion that ca. 3 counterions bound to dPGS were released upon complex formation. The gain in entropy Δ G ci by this counterion-release scales logarithmically with salt concentration and is the main driving force for binding. The temperature dependence of Δ G o was analyzed by the nonlinear van't Hoff plot, taking into account a finite heat capacity change Δ C p ,vH . This evaluation led to the binding enthalpy Δ H vH and the binding entropy Δ S vH . Both quantities varied strongly with temperature and even changed sign, but they compensated each other throughout the entire range of temperature. Coarse-grained computer simulations with explicit salt and implicit water were used to obtain the binding free energies that agreed with ITC results. Thus, electrostatic factors were the driving forces for binding whereas all hydration contributions leading to the strongly varying Δ H vH and Δ S vH canceled out. The calorimetric enthalpy Δ H ITC measured directly by ITC differed largely from Δ H vH . ITC measurements done in two buffer systems with different ionization enthalpies revealed that binding was linked to buffer ionization and a partial protonation of the protein., Competing Interests: The authors declare no competing financial interest.

Macromolecules based on dendritic or hyperbranched polyelectrolytes have been emerging as high potential candidates for biomedical applications. Here we study the charge and solvation structure of dendritic polyglycerol sulphate (dPGS) of generations 0 to 3 in aqueous sodium chloride solution by explicit-solvent molecular dynamics computer simulations. We characterize dPGS by calculating several important properties such as relevant dPGS radii, molecular distributions, the solvent accessible surface area, and the partial molecular volume. In particular, as the dPGS exhibits high charge renormalization effects, we address the challenges of how to obtain a well-defined effective charge and surface potential of dPGS for practical applications. We compare implicit- and explicit-solvent approaches in our all-atom simulations with the coarse-grained simulations from our previous work. We find consistent values for the effective electrostatic size (i.e., the location of the effective charge of a Debye-Hückel sphere) within all the approaches, deviating at most by the size of a water molecule. Finally, the excess chemical potential of water insertion into dPGS and its thermodynamic signature are presented and rationalized.

Dendritic polyelectrolytes constitute high potential drugs and carrier systems for biomedical purposes. Still, their biomolecular interaction modes, in particular those determining the binding affinity to proteins, have not been rationalized. We study the interaction of the drug candidate dendritic polyglycerol sulfate (dPGS) with serum proteins using isothermal titration calorimetry (ITC) interpreted and complemented with molecular computer simulations. Lysozyme is first studied as a well-defined model protein to verify theoretical concepts, which are then applied to the important cell adhesion protein family of selectins. We demonstrate that the driving force of the strong complexation, leading to a distinct protein corona, originates mainly from the release of only a few condensed counterions from the dPGS upon binding. The binding constant shows a surprisingly weak dependence on dPGS size (and bare charge) which can be understood by colloidal charge-renormalization effects and by the fact that the magnitude of the dominating counterion-release mechanism almost exclusively depends on the interfacial charge structure of the protein-specific binding patch. Our findings explain the high selectivity of P- and L-selectins over E-selectin for dPGS to act as a highly anti-inflammatory drug. The entire analysis demonstrates that the interaction of proteins with charged polymeric drugs can be predicted by simulations with unprecedented accuracy. Thus, our results open new perspectives for the rational design of charged polymeric drugs and carrier systems.

The immobilization of bovine serum albumins (BSA) onto cationic spherical polyelectrolyte brushes (SPB) consisting of a solid polystyrene (PS) core and a densely grafted poly(2-aminoethyl methacrylate hydrochloride) (PAEMH) shell was studied by small-angle X-ray scattering (SAXS). The observed dynamics of adsorption of BSA onto SPB by time-resolved SAXS can be divided into two stages. In the first stage (tens of milliseconds), the added proteins as in-between bridge instantaneously caused the aggregation of SPB. Then BSA penetrated into the brush layer driven by electrostatic attractions, and reached equilibrium in the second stage (tens of seconds). The amount of BSA immobilized onto brush layer reached the maximum when pH was increased to about 6.1 and BSA concentration to 10 g/L. The cationic SPB were confirmed to provide stronger adsorption capacity for BSA compared to anionic ones.

We study the adsorption of charged patchy particle models (CPPMs) on a thin film of a like-charged and dense polyelectrolyte (PE) brush (of 50 monomers per chain) by means of implicit-solvent, explicit-salt Langevin dynamics computer simulations. Our previously introduced set of CPPMs embraces well-defined one- and two-patched spherical globules, each of the same net charge and (nanometer) size, with mono- and multipole moments comparable to those of small globular proteins. We focus on electrostatic effects on the adsorption far away from the isoelectric point of typical proteins, i.e., where charge regulation plays no role. Despite the same net charge of the brush and globule, we observe large binding affinities up to tens of the thermal energy, k B T, which are enhanced by decreasing salt concentration and increasing charge of the patch(es). Our analysis of the distance-resolved potentials of mean force together with a phenomenological description of all leading interaction contributions shows that the attraction is strongest at the brush surface, driven by multipolar, Born (self-energy), and counterion-release contributions, dominating locally over the monopolar and steric repulsions.

The leading nonlinear stress response in a periodically strained concentrated colloidal dispersion is studied experimentally and by theory. A thermosensitive microgel dispersion serves as well-characterized glass-forming model, where the stress response at the first higher harmonic frequency (3ω for strain at frequency ω) is investigated in the limit of small amplitude. The intrinsic nonlinearity at the third harmonic exhibits a scaling behavior which has a maximum in an intermediate frequency window and diverges when approaching the glass transition. It captures the (in-) stability of the transient elastic structure. Elastic stresses in-phase with the third power of the strain dominate the scaling. Our results qualitatively differ from previously derived scaling behavior in dielectric spectroscopy of supercooled molecular liquids. This might indicate a dependence of the nonlinear response on the symmetry of the external driving under time reversal.

In this study, dispersible mesoporous nitrogen-doped hollow carbon nanoplates have been synthesized as a new anisotropic carbon nanostructure using gibbsite nanoplates as templates. The gibbsite-silica core-shell nanoplates were first prepared before the gibbsite core was etched away. Dopamine as carbon precursor was self-polymerized on the hollow silica nanoplates surface assisted by sonification, which not only favors a homogeneous polymer coating on the nanoplates but also prevents their aggregation during the polymerization. Individual silica-polydopamine core-shell nanoplates were immobilized in a silica gel in an insulated state via a silica nanocasting technique. After pyrolysis in a nanoconfine environment and elimination of silica, discrete and dispersible hollow carbon nanoplates are obtained. The resulted hollow carbon nanoplates bear uniform hexagonal morphology with specific surface area of 460 m 2 ·g -1 and fairly accessible small mesopores (∼3.8 nm). They show excellent colloidal stability in aqueous media and are applied as electrode materials for symmetric supercapacitors. When using polyvinylimidazolium-based nanoparticles as a binder in electrodes, the hollow carbon nanoplates present superior performance in parallel to polyvinylidene fluoride (PVDF) binder.

We present an operando neutron reflectometry study on the electrochemical incorporation of lithium into crystalline silicon for battery applications. Neutron reflectivity is measured from the ⟨100⟩ surface of a silicon single crystal which is used as a negative electrode in an electrochemical cell. The strong scattering contrast between Si and Li due to the negative scattering length of Li leads to a precise depth profile of Li within the Si anode as a function of time. The operando cell can be used to study the uptake and the release of Li over several cycles. Lithiation starts with the formation of a lithium enrichment zone during the first charge step. The uptake of Li can be divided into a highly lithiated zone at the surface (skin region) (x ∼ 2.5 in LixSi) and a much less lithiated zone deep into the crystal (growth region) (x ∼ 0.1 in LixSi). The total depth of penetration was less than 100 nm in all experiments. The thickness of the highly lithiated zone is the same for the first and second cycle, whereas the thickness of the less lithiated zone is larger for the second lithiation. A surface layer of lithium (x ∼ 1.1) remains in the silicon electrode after delithiation. Moreover, a solid electrolyte interface is formed and dissolved during the entire cycling. The operando analysis presented here demonstrates that neutron reflectivity allows the tracking of the kinetics of lithiation and delithiation of silicon with high spatial and temporal resolution.

We present a detailed theory for the total reaction rate constant of a composite core-shell nanoreactor, consisting of a central solid core surrounded by a hydrogel layer of variable thickness, where a given number of small catalytic nanoparticles are embedded at prescribed positions and are endowed with a prescribed surface reaction rate constant. Besides the precise geometry of the assembly, our theory accounts explicitly for the diffusion coefficients of the reactants in the hydrogel and in the bulk as well as for their transfer free energy jump upon entering the hydrogel shell. Moreover, we work out an approximate analytical formula for the overall rate constant, which is valid in the physically relevant range of geometrical and chemical parameters. We discuss in depth how the diffusion-controlled part of the rate depends on the essential variables, including the size of the central core. In particular, we derive some simple rules for estimating the number of nanocatalysts per nanoreactor for an efficient catalytic performance in the case of small to intermediate core sizes. Our theoretical treatment promises to provide a very useful and flexible tool for the design of superior performing nanoreactor geometries with optimized nanoparticle load.

Lithium sulfur cells are the most promising candidate for the post lithium-ion battery era. Their major drawback is rapid capacity fading attributed to the complex electrochemical processes during charge and discharge which are not known precisely. Here we present for the first time a multidimensional operando measurement by combining X-ray radiography with impedance spectroscopy while galvanostatically charging and discharging a lithium sulfur cell. The formation of macroscopic sulfur crystals at the end of charge can be seen directly by X-ray radiography. These crystals can be assigned to stable α-sulfur (rhombic) and metastable β-sulfur (monoclinic) by their characteristic crystal habit. These crystal structures with a length of more than 1 mm form and dissolve rapidly during cycling. Their appearance is accompanied by characteristic signals in impedance spectroscopy. Macroscopic crystals of Li2S cannot be observed in full agreement with earlier studies by operando X-ray diffraction. In addition, X-ray radiography reveals non-wetted areas on the carbon cathode. These regions grow during discharge and are reduced during charge. The area of these electrochemically inactive spots is inversely proportional to discharge capacity.

The analysis of sulfur distribution in porous carbon/sulfur nanocomposites using small-angle X-ray scattering (SAXS) is presented. Ordered porous CMK-8 carbon was used as the host matrix and gradually filled with sulfur (20-50 wt %) via melt impregnation. Owing to the almost complete match between the electron densities of carbon and sulfur, the porous nanocomposites present in essence a two-phase system and the filling of the host material can be precisely followed by this method. The absolute scattering intensities normalized per unit of mass were corrected accounting for the scattering contribution of the turbostratic microstructure of carbon and amorphous sulfur. The analysis using the Porod parameter and the chord-length distribution (CLD) approach determined the specific surface areas and filling mechanism of the nanocomposite materials, respectively. Thus, SAXS provides comprehensive characterization of the sulfur distribution in porous carbon and valuable information for a deeper understanding of cathode materials of lithium-sulfur batteries.

Protein microtubule is a significant self-assembled architecture found in nature with crucial biological functions. However, mimicking protein microtubules with precise structure and controllable self-assembly behavior remains highly challenging. In this work, we demonstrate that by using dual supramolecular interactions from a series of well-designed ligands, i.e., protein-sugar interaction and π-π stacking, highly homogeneous protein microtubes were achieved from tetrameric soybean agglutinin without any chemical or biological modification. Using combined cryo-EM single-particle reconstruction and computational modeling, the accurate structure of protein microtube was determined. The helical protein microtube is consisted of three protofilaments, each of which features an array of soybean agglutinin tetramer linked by the designed ligands. Notably, the microtubes resemble the natural microtubules in their structural and dynamic features such as the shape and diameter and the controllable and reversible assembly behavior, among others. Furthermore, the protein microtubes showed an ability to enhance immune response, demonstrating its great potential for biological applications.

The peptide amyloid-β (Aβ) interacts with membranes of cells in the human brain and is associated with Alzheimer's disease (AD). The intercalation of Aβ in membranes alters membrane properties, including the structure and lipid dynamics. Any change in the membrane lipid dynamics will affect essential membrane processes, such as energy conversion, signal transduction and amyloid precursor protein (APP) processing, and may result in the observed neurotoxicity associated with the disease. The influence of this peptide on membrane dynamics was studied with quasi-elastic neutron scattering, a technique which allows a wide range of observation times from picoseconds to nanoseconds, over nanometer length scales. The effect of the membrane integral neurotoxic peptide amyloid-β, residues 22-40, on the in- and out-of-plane lipid dynamics was observed in an oriented DMPC/DMPS bilayer at 15 °C, in its gel phase, and at 30 °C, near the phase transition temperature of the lipids. Near the phase-transition temperature, a 1.5 mol% of peptide causes up to a twofold decrease in the lipid diffusion coefficients. In the gel-phase, this effect is reversed, with amyloid-β(22-40) increasing the lipid diffusion coefficients. The observed changes in lipid diffusion are relevant to protein-protein interactions, which are strongly influenced by the diffusion of membrane components. The effect of the amyloid-β peptide fragment on the diffusion of membrane lipids will provide insight into the membrane's role in AD.

Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL(2-)) or phosphatidylcerine (PS(1-)) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains ("spherical polycationic brushes", SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometry, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo-TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into "islands". (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as ν) that ensures the structural integrity of liposomes upon complexation: ν=0.3 for liposomes with conically-shaped CL(2-) and ν=0.5 for liposomes with anionic cylindrically-shaped PS(1-). (c) The number of intact liposomes per SPB particle varies from 40 for (ν=0.1) to 13 (ν=0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents when the pH is reduced from 7.0 to 5.0. The results allow loaded liposomes to be concentrated within a rather small volume and, thereby, the preparation of multi-liposomal containers of promise in the drug delivery field., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We present a detailed study of the catalytic activity of Au/Pd nanoalloys with Au : Pd molar ratio 75 : 25 synthesized using spherical polyelectrolyte brushes (SPB) as carrier system. The reduction of 4-nitrophenol (Nip) by sodium borohydride (BH4(-)) has been used as a model reaction. This reaction proceeds in two steps: 4-nitrophenol is first reduced to 4-hydroxylaminophenol which in a second step is reduced to the final product 4-aminophenol. Both steps of the reaction proceed on the surface of the nanoparticles (Langmuir-Hinshelwood-mechanism). We use this model to analyze the experimental data obtained by catalysis with the Au/Pd-nanoalloys. Good agreements between theory and experiments were found up to 30% conversion of Nip. The kinetic parameters were compared with the data derived from neat Au and Pd nanoparticles immobilized in the same SPB carrier system. The addition of 25% molar ratio of Pd to the nanoalloys increases the reaction rate of the first step nearly 10 times compared with that of SPB-Au and 60 times compared with that of SPB-Pd. Analysis of the nanoalloy by high-resolution transmission electron microscopy suggests that the surface defects of the nanoalloys play an important role for the enhanced catalytic activity.

We investigate the nonequilibrium behavior of dense, plastic-crystalline suspensions of mildly anisotropic colloidal hard dumbbells under the action of an oscillatory shear field by employing Brownian dynamics computer simulations. In particular, we extend previous investigations, where we uncovered nonequilibrium phase transitions, to other aspect ratios and to a larger nonequilibrium parameter space, that is, a wider range of strains and shear frequencies. We compare and discuss selected results in the context of scattering and rheological experiments. Both simulations and experiments demonstrate that the previously found transitions from the plastic crystal phase with increasing shear strain also occur at other aspect ratios. We explore the transition behavior in the strain-frequency phase and summarize it in a nonequilibrium phase diagram. Additionally, the experimental rheology results hint at a slowing down of the colloidal dynamics with higher aspect ratio.

We study shear effects in solid-supported lipid membrane stacks by simultaneous combined in-situ neutron reflectivity (NR) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The stacks mimic the terminal surface-active phospholipid (SAPL) coatings on cartilage in mammalian joints. Piles of 11 bilayer membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are immobilized at the interface of the solid silicon support and the liquid D2O backing phase. We replace the natural hyaluronic acid (HA) component of synovial fluid by a synthetic substitute, namely, poly(allylamine hydrochloride) (PAH), at identical concentration. We find the oligolamellar DMPC bilayer films strongly interacting with PAH resulting in a drastic increase of the membranes d spacing (by a factor of ∼5). Onset of shear causes a buckling-like deformation of the DMPC bilayers perpendicular to the applied shear field. With increasing shear rate we observe substantially enhanced water fractions in the membrane slabs which we attribute to increasing fragmentation caused by Kelvin-Helmholtz-like instabilities parallel to the applied shear field. Both effects are in line with recent theoretical predictions on shear-induced instabilities of lipid bilayer membranes in water (Hanasaki, I.; Walther, J. H.; Kawano, S.; Koumoutsakos, P. Phys. Rev. E 2010, 82, 051602). With the applied shear the interfacial lipid linings transform from their gel state Pβ' to their fluid state Lα. Although in chain-molten state with reduced bending rigidity the lipid layers do not detach from their solid support. We hold steric bridging of the fragmented lipid bilayer membranes by PAH molecules responsible for the unexpected mechanical stability of the DMPC linings.

We report a facile method to synthesize anisotropic platelike gibbsite-polymer core-shell particles. Dopamine is self-polymerized on the surface of gibbsite nanoplates and forms a homogeneous layer on it. Transmission electron microscopy characterization of the resulting latexes demonstrates the formation of well-defined platelike core-shell particles. Reaction time and ultrasonification are found to be important factors to control the thickness of the polymer shell and avoid aggregation. Good control over the platelike morphology and 100% encapsulation efficiency have been achieved via this novel route. The resulting well-defined gibbsite-polydamine (G-PDA) core-shell nanoplates show excellent colloidal stability and can form opal-like columnar crystal with iridescent Bragg reflection after modest centrifugation. In addition, G-PDA core-shell nanoplates can serve both as reductant and stabilizer for the generation of Au nanoparticles (NPs) in situ. Au NPs with tunable size have been formed on the G-PDA particle surface, which show efficient catalytic activity for the reduction of 4-nitrophenol and Rhodamine B (RhB) in the presence of borohydride. Such nanocatalysts can be easily deposited on silicon substrate by spin-coating due to the large contact area of platelike G-PDA particles and the strong adhesive behavior of the PDA layer. The substrate-deposited nanocatalyst can be easily recycled which show excellent reusability for the reduction of RhB.

We study the pair complexation of a single, highly charged polyelectrolyte (PE) chain (of 25 or 50 monomers) with like-charged patchy protein models (CPPMs) by means of implicit-solvent, explicit-salt Langevin dynamics computer simulations. Our previously introduced set of CPPMs embraces well-defined zero-, one-, and two-patched spherical globules each of the same net charge and (nanometer) size with mono- and multipole moments comparable to those of globular proteins with similar size. We observe large binding affinities between the CPPM and the like-charged PE in the tens of the thermal energy, kBT, that are favored by decreasing salt concentration and increasing charge of the patch(es). Our systematic analysis shows a clear correlation between the distance-resolved potentials of mean force, the number of ions released from the PE, and CPPM orientation effects. In particular, we find a novel two-site binding behavior for PEs in the case of two-patched CPPMs, where intermediate metastable complex structures are formed. In order to describe the salt-dependence of the binding affinity for mainly dipolar (one-patched) CPPMs, we introduce a combined counterion-release/Debye-Hückel model that quantitatively captures the essential physics of electrostatic complexation in our systems.

We present a comprehensive study of the interaction of human serum albumin (HSA) with poly(acrylic acid) (PAA; number average degree of polymerization: 25) in aqueous solution. The interaction of HSA with PAA is studied in dilute solution as a function of the concentration of added salt (20-100 mM) and temperature (25-37 °C). Isothermal titration calorimetry (ITC) is used to analyze the interaction and to determine the binding constant and related thermodynamic data. It is found that only one PAA chain is bound per HSA molecule. The free energy of binding ΔGb increases with temperature significantly. ΔGb decreases with increasing salt concentration and is dominated by entropic contributions due to the release of bound counterions. Coarse-grained Langevin computer simulations treating the counterions in an explicit manner are used to study the process of binding in detail. These simulations demonstrate that the PAA chains are bound in the Sudlow II site of HSA. Moreover, ΔGb is calculated from the simulations and found to be in very good agreement with the measured data. The simulations demonstrate clearly that the driving force of binding is the release of counterions in full agreement with the ITC-data.

We study the structure and viscoelastic behavior of 3D plastic crystals of colloidal dumbbells in an oscillatory shear field based on a combination of small-angle neutron scattering experiments under shear (rheo-SANS) and Brownian dynamics computer simulations. Sterically stabilized dumbbell-shaped microgels are used as hard dumbbell model systems which consist of dumbbell-shaped polystyrene (PS) cores and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) shells. Under increasing shear strain, a discontinuous transition is found from a twinned-fcc-like crystal to a partially oriented sliding-layer phase with a shear-molten state in between. In the novel partially oriented sliding-layer phase, the hard dumbbells exhibit a small but finite orientational order in the shear direction. We find that this weak correlation is sufficient to perturb the nature of the nonequilibrium phase transition as known for hard sphere systems. The discontinuous transition for hard dumbbells is observed to be accompanied by a novel yielding process with two yielding events in its viscoelastic shear response, while only a single yielding event is observed for sheared hard spheres. Our findings will be useful in interpreting the shear response of anisotropic colloidal systems and in generating novel colloidal crystals from anisotropic systems with applications in colloidal photonics.

Transient stress-strain relations close to the colloidal glass transition are obtained within the integration through transients framework generalizing mode coupling theory to flow driven systems. Results from large-scale numerical calculations are quantitatively compared to experiments on thermosensitive microgels, which reveals that theory captures the magnitudes of stresses semi-quantitatively even in the nonlinear regime, but overestimates the characteristic strain where plastic events set in. The former conclusion can also be drawn from flow curves, while the latter conclusion is supported by a comparison to single particle motion measured by confocal microscopy. The qualitative picture, as previously obtained from simplifications of the theory in schematic models, is recovered by the quantitative solutions of the theory for Brownian hard spheres.