Molecular Insights into the Self-Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined ß-Sheets.

Suckerin in squid sucker ring teeth is a block-copolymer peptide comprised of two repeating modules-the alanine and histidine-rich M1 and the glycine-rich M2. Suckerin self-assemblies display excellent thermo-plasticity and pH-responsive properties, along with the high biocompatibility, biodegradability, and sustainability. However, the self-assembly mechanism and the detailed role of each module are still elusive, limiting the capability of applying and manipulating such biomaterials. Here, the self-assembly dynamics of the two modules and two minimalist suckerin-mimetic block-copolymers, M1-M2-M1 and M2-M1-M2, in silico is investigated. The simulation results demonstrate that M2 has a stronger self-association but weaker ß-sheet propensities than M1. The high self-assembly propensity of M2 allows the minimalist block-copolymer peptides to coalesce with microphase separation, enabling the formation of nanoconfined ß-sheets in the matrix formed by M1-M2 contacts. Since these glycine-rich fragments with scatted hydrophobic and aromatic residues are building blocks of many other block-copolymer peptides, the study suggests that these modules function as the "molecular glue" in addition to the flexible linker or spacer to drive the self-assembly and microphase separation. The uncovered molecular insights may help understand the structure and function of suckerin and also aid in the design of functional block-copolymer peptides for nanotechnology and biomedicine applications.

Simulations of 3-arm polyelectrolyte star brushes under external electric fields.

Langevin dynamics (LD) simulations have been performed to study the conformations and stratification of grafted three-arm polyelectrolyte (PE) stars in response to external electric fields. The grafted chains with neutral stems and fully charged branches were immersed in a salt-free solution sandwiched between the grafting electrode and a second oppositely charged electrode. The branching points of neutral-stem PE brushes at low grafting densities exhibit a bimodal distribution normal to the grafting electrode. With increasing grafting density, the molecular conformations in the brush layer become more complex with the emergence of multi-mode distributions of the branching point monomers. Under strong electric fields, the fraction of grafted chains with either nearly completely stretched stems or collapsed branches onto the grafting electrode gradually decreases with increasing grafting density due to the stronger electrostatic screening from counterions and monomer charges at higher grafting densities. Simulation results revealed that a collapsing electric field promotes the stratification within the brush layer, leading to high degrees of charge overcompensation from charged monomers collapsed onto the oppositely charged grafting electrode. An approximate analytical self-consistent field model was developed to examine the stratification within the brush layer. Regarding the fraction of grafted chains with the free branches in the upper layer, the prediction of the analytical model qualitatively agrees with the simulation results.

Simulations of polymer brushes with charged end monomers under external electric fields.

Using Langevin dynamics simulations, the response of neutral polymer brushes with charged terminal monomers to external electric fields has been investigated. The external electric field is equivalent to the field generated by the opposite surface charges on two parallel electrodes. The effects of charge valence of terminal monomers on the structure of double layers and overall charge balance near the two electrodes were examined. Using the charge density distributions obtained from simulations, the total electric field normal to the electrodes was calculated by numerically solving the Poisson equation. Under external electric fields, the total electric field across the two electrodes is highly non-uniform and in certain regions within the brush, the total electric field nearly vanishes. The probability distribution of electric force acting on one charged terminal monomer was obtained from simulations and how it affects the probability density distribution of terminal monomers was analyzed. The response of polymer brushes with charged terminal monomers to a strongly stretching external electric field was compared with that of uniformly charged polymer brushes.

Numerical investigation of the contraction of neutral-charged diblock copolymer brushes in electric fields.

Using self-consistent field theory (SCFT), the contraction of neutral-charged A-B diblock copolymer brushes in electric fields generated by opposite surface charges on two parallel electrodes has been numerically investigated. The diblock copolymer chains were grafted with the free end of the neutral block to one electrode and immersed in a salt-free solution sandwiched between the two electrodes. The numerical results reveal that the charged monomers, A-B joint segment and the tail exhibit bimodal distributions under external electric fields, which are absent for homopolymer polyelectrolyte brushes. The dependences of the relative populations and peak positions of the two modes on various parameters such as block ratio, grafting density, chain length and strength of the applied electric field were systematically examined and the underlining mechanisms were elucidated. It was found in this study that, if the total amount of surface charges on the grafting electrode is no more than that of the counter-ions in the system, overall charge neutrality is generally maintained inside the brushes when including the contribution of surface charges on the grafting electrode. In such a case, the counter-ions expelled from the brushes are highly enriched in the immediate vicinity of the second electrode and an approximate charge balance between these expelled counter-ions and the opposite surface charges on the second electrode is achieved.

Numerical self-consistent field theory study of the response of strong polyelectrolyte brushes to external electric fields.

The response of strong polyelectrolyte (PE) brushes grafted on an electrode to electric fields generated by opposite surface charges on the PE-grafted electrode and a second parallel electrode has been numerically investigated by self-consistent field theory. The influences of grafting density, average charge fraction, salt concentration, and mobile ion size on the variation of the brush height against an applied voltage bias were investigated. In agreement with molecular dynamics simulation results, a higher grafting density requires a larger magnitude of voltage bias to achieve the same amount of relative change in the brush height. In the experimentally relevant parameter regime of the applied voltage, the brush height becomes insensitive to the voltage bias when the grafting density is high. Including the contribution of surface charges on the grafting electrode, overall charge neutrality inside the PE brushes is generally maintained, especially for PE brushes with high grafting density and high average charge fraction. Our numerical study further reveals that the electric field across the two electrodes is highly non-uniform because of the complex interplay between the surface charges on the electrodes, the charges on the grafted PE chains, and counterions.

Numerical study of weak polybase brushes grafted on neutral or charged spherical surface by the self-consistent field theory.

The self-consistent field theory (SCFT) is employed to numerically study the response of weak polybase type polymer chains grafted on a sphere to electric fields generated by the uniform positive or negative charges on the grafting substrate in the planar polyelectrolyte brush limit. Also the effect of curvature of the grafting sphere on the brush height of weak polybase brushes in the absence of surface charges is investigated. The numerical study reveals interesting and nontrivial dependence of the brush height on the radius of the grafting substrate. Consistent with experimental results, in the parameter range of the surface charge density examined, the brush height is found to be independent of the applied electric field at intermediate and high grafting densities. At relatively low grafting density, the applied negative surface charge which is termed as negative bias in this study results in a reduction of the brush height. At rather low grafting density, the positive bias corresponding to applied positive surface charges can lead to a slight increase in the brush height. The underlining mechanism governing the response of weak polybase brushes to the applied electric field is elucidated.

A numerical study of the phase behaviors of drug particle/star triblock copolymer mixtures in dilute solutions for drug carrier application.

The complex microstructures of drug particle/ABA star triblock copolymer in dilute solutions have been investigated by a theoretical approach which combines the self-consistent field theory and the hybrid particle-field theory. Simulation results reveal that, when the volume fraction of drug particles is smaller than the saturation concentration, the drug particle encapsulation efficiency is 100%, and micelle loading capacity increases with increasing particle volume fraction. When the volume fraction of drug particles is equal to the saturation concentration, the micelles attain the biggest size, and micelle loading capacity reaches a maximum value which is independent of the copolymer volume fraction. When the volume fraction of drug particles is more than the saturation concentration, drug particle encapsulation efficiency decreases with increasing volume fraction of drug particles. Furthermore, it is found that the saturation concentration scales linearly with the copolymer volume fraction. The above simulation results are in good agreement with experimental results.

The numerical study of the adsorption of flexible polyelectrolytes with the annealed charge distribution onto an oppositely charged sphere by the self-consistent field theory.

The adsorption of flexible polyelectrolytes (PEs) with the annealed charge distribution onto an oppositely charged sphere immersed in a PE solution is studied numerically with the continuum self-consistent field theory. The numerical study reveals interesting scaling relationships between the boundary layer thickness and the surface charge density of the sphere as well as the degree of ionization of the monomers of the PE chains in the bulk solution. The dependences of the degree of charge compensation of the total amount of charges on adsorbed PE chains over the surface charges upon various system parameters are investigated. In particular, the effect of the radius of the charged sphere on the degree of charge compensation is carefully examined. The numerical study indicates that the curvature effect is closely related to the surface electric potential of the charged sphere. Moreover, in this study of the adsorption of PEs with the annealed charge distribution, a comparison with the corresponding case for PEs with the smeared charge distribution in terms of the boundary layer scaling law and the degree of charge compensation is also presented.

Biapenem versus meropenem in the treatment of bacterial infections: a multicenter, randomized, controlled clinical trial.

BACKGROUND & OBJECTIVES: Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China. METHODS: Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed. RESULTS: A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%). INTERPRETATION & CONCLUSIONS: Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.

The interplay of the polyelectrolyte-surface electrostatic and non-electrostatic interactions in the polyelectrolytes adsorption onto two charged objects--a self-consistent field study.

The continuum self-consistent field (SCF) theory is applied to the study of the adsorption of flexible polyelectrolytes (PEs) onto the surfaces of two parallel and infinitely long charged columns, taking into account the short-range monomer-surface non-Coulombic interaction. Due to the complex interplay between the electrostatic and surface interactions, very interesting PE adsorption behaviors in terms of the degree of charge compensation and the bridging chain conformation are found from the numerical solution of the SCF equations. The screening-enhanced salt effect and the permanent adsorption of PEs, irrespectively of the salt concentration, emerge in the presence of the monomer-surface non-electrostatic interaction. The numerical results reveal that, for relatively weak monomer-surface interactions, the degree of charge compensation decreases with increasing monomer-surface interaction. Numerical result shows that, for the strength of monomer-surface interaction above the desorption-adsorption critical value and in a salt-free solution, the total amount of the adsorbed PE chains is linearly proportional to the surface charge density in the high PE charge fraction regime.

The self-consistent field study of the adsorption of flexible polyelectrolytes onto two charged nano-objects.

The continuum self-consistent field theory (SCFT) is applied to the study of the adsorption of flexible polyelectrolyte (PE) onto the surfaces of two two-dimensional charged square objects with a constant electric field strength immersed in a weakly charged polyelectrolyte solution. The dependences of the different chain conformations, that is, bridging, loop, tail, and train, and in particular, the bridging chain conformation, on various system parameters (the charge fraction of the PE chains, the surface charge density, the object size, the salt concentration, etc.) are investigated. The efficient multigrid method is adopted to numerically solve the modified diffusion equation and the Poisson equation. It is found that the thickness L(B) of the boundary layer of the adsorbed PE chains is independent of the chain length and scales with the surface charge density σ and the fraction of charges on PE chains α(P) as L(B) ~ σ(-0.36) and L(B) ~ α(P)(-0.36), respectively. Simulation results reveal that the total amount of bridging chain conformation in the system scales linearly with respect to the size of the charge objects and scales linearly with the chain length in the long polymer chain regime. Simulation results reveal that the total amount of the bridging chain conformation in the system scales with the charge fraction of PE chains as a power law and the scaling exponent is dependent on all of the other system parameters. Simulation results show that the total amount of charges on the adsorbed chains in the system can overcompensate the surface charges for relatively long chains with high charge fractions.

Self-consistent-field and hybrid particle-field theory simulation of confined copolymer and nanoparticle mixtures.

In this paper, we used combined self-consistent-field and hybrid particle-field theory to explore the self-assembly behavior of diblock copolymer-nanoparticle mixtures confined between two concentric circular walls. The simulation reveals that the structural frustration, the loss of conformational entropy of the copolymer, and the radii of the two concentric circles have great influence on the morphologies of the system. We also discuss the underlying mechanism of controlling the self-assembly of such a system in terms of enthalpic interaction between particles and copolymers, steric repulsive interactions between particles, and the conformational entropy of copolymers, and a representative phase diagram in terms of block ratio and the particle volume fraction is constructed. This study suggests a route to help experimentalists better create high-performance nanodevices.

The finite size effect of monomer units on the electrostatics of polyelectrolyte solutions.

The effective interactions between two test counterions and two test solvent dipoles in a semidilute/concentrated weakly charged polyelectrolyte solution are studied using the field-theoretical approach on the mean-field level. From the effective Hamiltonians in terms of the two test counterions and the two test solvent dipoles, respectively, analytical expressions for the effective interactions in the real space are derived. It is unambiguously demonstrated that, at a Theta solvent condition, both the effective interactions between two counterions and two parallel-oriented solvent dipoles consist of an attractive part at intermediate distances of separation. As the electrostatic screening effect from counterions and salt ions quantified by the Debye-Hückel screening parameter becomes stronger, the magnitude of the attraction decreases and the minimum of the attractive profile shift to a shorter distance of separation. On the other hand, when the excluded volume effect is dominant, the effective interactions are purely repulsive. This nontrivial and seemingly counterintuitive result originates from the finite size effect of the monomer units of the polymer chains on the electrostatics of the polyelectrolyte solution. As the size of the monomer units goes to zero, at the Theta solvent condition, the effective interactions between two counterions and two parallel-oriented solvent dipoles are purely repulsive.

Phase behaviors of diblock copolymer-nanoparticle films under nanopore confinement.

We employ self-consistent-field and density-functional theories to simulate the phase behaviors of diblock copolymer-nanoparticle mixtures confined in a two-dimensional circular pore. By varying the block ratio, the size of the pore, and the particle concentration, rich phase structures are discovered. It is shown that the structural frustration, the loss of conformational entropy of the polymer chains under confinement, the curvature of the pore, and the steric packing effect of the particles play important roles in determining the morphologies of the nanocomposites under circular confinement. It is found that the increase in the particle concentration can promote the transformation of concentric lamellas to the cylindrical domains. Our results suggest effective ways to stabilize the phase orderings of diblock copolymer-nanoparticle mixtures under two-dimensional circular confinement.

Enhanced orientational ordering of water dipoles in uniaxially stretched hydrogels.

The electrostatics and density correlations of dipolar solvent molecules in weakly charged polyelectrolyte solutions and charged gels are studied using a field-theoretical approach. For miscible dipolar solvent mixtures, an exact expression for the effective dielectric permittivity is obtained on the mean-field level, which depends upon the individual volume of each solvent species before mixing and the final volume of the mixture. If the effect of volume change is small during mixing, the dielectric permittivity is approximately equal to the volume-averaged dielectric permittivity of the individual components of the dipolar solvent mixture. It is found that the electrostatic interaction between the dipolar solvent molecules or any charged species in the polyelectrolyte solution is screened by both counterions (and co-ions if salt is added) and polyions, and there exists a total screening length for any charged species in the system which contains the contribution from the polyions. The screening from the polyions is as important as that from the counterions on the length scale of the polymer coil size. For uniaxially stretched charged gels, it is shown that there is an enhanced orientational ordering of the dipolar solvent molecules along the stretching direction, and the correlation length (r(cor)) of this enhanced orientational ordering is about the product of the total screening length (xi(-1)) due to the counterions and polyions times the square root of the dielectric constant of the medium, that is, r(cor)approximately equal to (epsilon(r)xi(-1))1/2.

Phase-field modeling of wetting on structured surfaces.

We study the dynamics and equilibrium profile shapes of contact lines for wetting in the case of a spatially inhomogeneous solid wall with stripe defects. Using a phase-field model with conserved dynamics, we first numerically determine the contact line behavior in the case of a stripe defect of varying widths. For narrow defects, we find that the maximum distortion of the contact line and the healing length is related to the defect width, while for wide defects, it saturates to constant values. This behavior is in quantitative agreement with the experimental data. In addition, we examine the shape of the contact line between two stripe defects as a function of their separation. Using the phase-field model, we also analytically estimate the contact line configuration and find good qualitative agreement with the numerical results.