Phase-separated Polymer Research Articles

Rigidity enhances a magic-number effect in polymer phase separation

Cells possess non-membrane-bound bodies, many of which are now understood as phase-separated condensates. One class of such condensates is composed of two polymer species, where each consists of repeated binding sites that interact in a one-to-one fashion with the binding sites of the other polymer. Biologically-motivated modeling revealed that phase separation is suppressed by a “magic-number effect” which occurs if the two polymers can form fully-bonded small oligomers by virtue of the number of binding sites in one polymer being an integer multiple of the number of binding sites of the other. Here we use lattice-model simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one of the polymer species has a rigid shape that allows for multiple distinct bonding conformations. Moreover, if one species is rigid, the effect is robust over a much greater range of relative concentrations of the two species.

Tunable confinement of Cu-Zn bimetallic oxides in carbon nanofiber networks by thermal diffusion for lithium-ion battery

In terms of solving the phase separation of metal oxides and polymer derived carbon matrix during the carbonization process, two active metal oxides with different thermal diffusion features are simultaneously introduced. The agglomeration and migration of copper-based species during the carbonization process are well suppressed by the existence of homogenous ZnO distributed in carbon matrix with less migration ability. The unique carbon-confined Cu-Zn bimetallic oxides films are constructed via a facile electrospinning method and subsequently annealing process. Taking advantage of the suppressive effect of ZnO, the agglomeration and migration of copper-based particles are restrained and thus realizes the size regulation of Cu2O/Cu particles as well as the confinement in carbon nanofibers. Our designed architecture not only maintains the intrinsic interface properties of carbon nanofiber, but also distinctively enhances a highly reversible lithium-ion storage nature. Moreover, the preparation technique can be applied for constructing self-supported flexible electrodes without the additional current collector, seasonably satisfying the requirement of flexible electronics industry and effectively avoiding the employment of superfluous electrode redundancy.

On the relations of phase separation and Hi-C maps to epigenetics.

The relationship between compartmentalization of the genome and epigenetics is long and hoary. In 1928, Heitz defined heterochromatin as the largest differentiated chromatin compartment in eukaryotic nuclei. Müller's discovery of position-effect variegation in 1930 went on to show that heterochromatin is a cytologically visible state of heritable (epigenetic) gene repression. Current insights into compartmentalization have come from a high-throughput top-down approach where contact frequency (Hi-C) maps revealed the presence of compartmental domains that segregate the genome into heterochromatin and euchromatin. It has been argued that the compartmentalization seen in Hi-C maps is owing to the physiochemical process of phase separation. Oddly, the insights provided by these experimental and conceptual advances have remained largely silent on how Hi-C maps and phase separation relate to epigenetics. Addressing this issue directly in mammals, we have made use of a bottom-up approach starting with the hallmarks of constitutive heterochromatin, heterochromatin protein 1 (HP1) and its binding partner the H3K9me2/3 determinant of the histone code. They are key epigenetic regulators in eukaryotes. Both hallmarks are also found outside mammalian constitutive heterochromatin as constituents of larger (0.1–5 Mb) heterochromatin-like domains and smaller (less than 100 kb) complexes. The well-documented ability of HP1 proteins to function as bridges between H3K9me2/3-marked nucleosomes contributes to polymer–polymer phase separation that packages epigenetically heritable chromatin states during interphase. Contacts mediated by HP1 ‘bridging’ are likely to have been detected in Hi-C maps, as evidenced by the B4 heterochromatic subcompartment that emerges from contacts between large KRAB-ZNF heterochromatin-like domains. Further, mutational analyses have revealed a finer, innate, compartmentalization in Hi-C experiments that probably reflect contacts involving smaller domains/complexes. Proteins that bridge (modified) DNA and histones in nucleosomal fibres—where the HP1–H3K9me2/3 interaction represents the most evolutionarily conserved paradigm—could drive and generate the fundamental compartmentalization of the interphase nucleus. This has implications for the mechanism(s) that maintains cellular identity, be it a terminally differentiated fibroblast or a pluripotent embryonic stem cell.

Salt-induced LCST-type thermal gelation of methylcellulose: quantifying non-specific interactions via fluctuation theory.

What drives the phase separation of water-soluble polymers in the presence of electrolytes was quantified on a molecular scale via statistical thermodynamic fluctuation theory. Quantifying polymer-water and polymer-salt interactions enabled us to identify the dominant interaction for phase separation. As a model system, the lower critical solution temperature (LCST) type thermal gelation of methylcellulose (MC) in aqueous salt solutions was chosen. The Kirkwood-Buff integrals for intermolecular interactions, calculated from the published calorimetric and volumetric data, showed that (1) the accumulation of salts around MC molecules (favourable interaction between salts and MC) inhibits thermal gelation and the depletion of salts from MC (unfavourable interaction between salts and MC) promotes the gelation, and (2) this salt-MC interaction is the dominant factor (50-100 times stronger than the water-MC interaction). This insight from the fluctuation theory is at odds with the age-old consensus regarding the driving force of thermal gelation: water structure change in the presence of salts induces the promotion or inhibition of thermal gelation. However, our conclusion is founded upon the ability of the fluctuation theory to quantify water-MC and salt-MC interaction independently via the Kirkwood-Buff integrals. Flory-Huggins (FH) theory, on the contrary, could not separate these two interactions owing to the lack of a thermodynamic degree of freedom because the lattice solution is assumed to be fully packed. In addition, the dominant contribution from salt depletion poses difficulty for the χ parameter, which is essentially the difference of contact energies. Our approach, requiring calorimetric and volumetric data alone as input, provides a simple and versatile method towards elucidating the effect of cosolvents on biopolymer phase separation of physiological importance.

Effect of polymer donor aggregation on the active layer morphology of amorphous polymer acceptor-based all-polymer solar cells

The aggregation tendency in solution of polymer donors is the dominant factor in the phase separation of semi-crystalline polymer donor/amorphous polymer acceptor blends in all-PSCs.

Mechanisms by Which Organic Solvent Exchange Transforms Responsive Pure Protein Hydrogels into Responsive Organogels.

Responsive pure protein organogel sensors and catalysts are fabricated by replacing the aqueous mobile phase of protein hydrogels with pure ethylene glycol (EG). Exchanging water for EG causes irreversible volume phase transitions (VPT) in bovine serum albumin (BSA) polymers; however, BSA hydrogel and organogel sensors show similar volume responses to protein-ligand binding. This work elucidates the mechanisms involved in this enabling irreversible VPT by examining the protein secondary structure, hydration, and protein polymer morphology. Organogel proteins retain their native activity because their secondary structure and hydration shell are relatively unperturbed by the EG exchange. Conversely, the decreasing solvent quality initiates polymer phase separation to minimize the BSA polymer surface area exposed to EG, thus decreasing distances between BSA polymer strands. These protein polymer morphology changes promote interprotein interactions between BSA polymer strands, which increase the effective polymer cross-link density and prevent organogel swelling as the mobile phase is exchanged back to water.

Fine-Tuning Semiconducting Polymer Self-Aggregation and Crystallinity Enables Optimal Morphology and High-Performance Printed All-Polymer Solar Cells.

Polymer aggregation and crystallization behavior play a crucial role in the performance of all-polymer solar cells (all-PSCs). Gaining control over polymer self-assembly via molecular design to influence bulk-heterojunction active-layer morphology, however, remains challenging. Herein, we show a simple yet effective way to modulate the self-aggregation of the commonly used naphthalene diimide (NDI)-based acceptor polymer (N2200), by systematically replacing a certain amount of alkyl side-chains with compact bulky side-chains (CBS). Specifically, we have synthesized a series of random copolymer (PNDI-CBSx) with different molar fractions (x = 0-1) of the CBS units and have found that both solution-phase aggregation and solid-state crystallinity of these acceptor polymers are progressively suppressed with increasing x as evidenced by UV-vis absorption, photoluminescence (PL) spectroscopies, thermal analysis, and grazing incidence X-ray scattering (GIWAXS) techniques. Importantly, as compared to the highly self-aggregating N2200, photovoltaic results show that blending of more amorphous acceptor polymers with donor polymer (PBDB-T) can enable all-PSCs with significantly increased PCE (up to 8.5%). The higher short-circuit current density (Jsc) results from the smaller polymer phase-separation domain sizes as evidenced by PL quenching and resonant soft X-ray scattering (R-SoXS) analyses. Additionally, we show that the lower crystallinity of the active layer is less sensitive to the film deposition methods. Thus, the transition from spin-coating to solution coating can be easily achieved with no performance losses. On the other hand, decreasing aggregation and crystallinity of the acceptor polymer too much reduces the photovoltaic performance as the donor phase-separation domain sizes increases. The highly amorphous acceptor polymers appear to induce formation of larger donor polymer crystallites. These results highlight the importance of a balanced aggregation strength between the donor and acceptor polymers to achieve high-performance all-PSCs with optimal active layer film morphology.

One-pot fabrication of polymer micro/nano-discs via phase separation and a roll-to-roll coating process

Disc-shaped particles are one of the unique and promising shapes that can improve adhesion to interfaces and can function as the key feature in various applications; e.g. injectable drug carriers. However, most of these methods include the shape deformation process from spheres to discs using various external stimuli or require multiple processing steps, which is complicated and has limitations in terms of continuous fabrication. We herein propose a novel method combining polymer blend phase separation and a roll-to-roll coating process to continuously fabricate polymer micro/nano-discs in a one-pot manner on a large-scale. The evaporation of solvent during a roll-to-roll coating process encourages the formation of homogenous island-like domains composed of the minor component dispersed in a matrix of the major component on a water-soluble polyvinyl alcohol (PVA) film. In fact, polyvinylpyrrolidone (PVP) was chosen as the major component since it dissolves in both water and chloroform. Another polymer, polystyrene (PS), as a minor component was dissolved in chloroform with PVP. A PVP and PVA matrix film can be easily washed out by water, and micro/nano-discs of the PS minor component can be obtained in a one-pot manner. This method is shown to be capable of continuously fabricating PS micro/nano-discs at a very high rate of ∼108 particles/min. The effects of fabrication conditions, such as the blend ratio and total polymer concentration on the dimensions of the PS discs were investigated, and a maximum aspect ratio (ratio between diameter and thickness) of 6.3 (diameter ∼830 nm, thickness ∼130 nm) was demonstrated. The method proposed in this study could provide a straightforward and time-saving way to continuously fabricate micro/nano-discs via polymer phase separation and a roll-to-roll coating process.

Effect of Temperature on the Cononsolvency of Poly(N-isopropylacrylamide) (PNIPAM) in Aqueous 1-Propanol

The wide range of applications of poly(N-isopropylacrylamide) (PNIPAM) is based on the temperature dependence of its coil-to-globule transition, which strongly relies on the solvent. Here, we focus on the cononsolvency effect of PNIPAM oligomers in aqueous 1-propanol mixtures that is studied by molecular dynamics simulations of single chains and membrane-like arrangements. The complete phase diagram is sketched from the radius of gyration of the simulated oligomers, and it is compared to that obtained from the hydrodynamic radius of PNIPAM microgels, finding a good agreement. At the water-rich region, the decrease of the lower critical solution temperature (LCST) with increasing cosolvent concentration is independent of the polymer length and concentration. In this region, the radius of gyration of our simulated oligomer is strongly temperature dependent and a coil–globule transition temperature is easily captured. Conversely, at the alcohol-rich region, simulations show a monotonically increasing radius of gyration of the oligomer with alcohol concentration, a radius that is practically independent of temperature. This finding is in line with a polymer phase separation, showing an upper critical solution temperature (UCST) for a small cosolvent concentration window, which depends on the polymer length and concentration. Hence, in this case, polymer–polymer effective interactions are key to phase separation instead of its single chain conformation, contrasting with the coil–globule transition. Indeed, we find a soft-coil like structure for the simulated oligomer around a propanol molar fraction of 0.24, which is close to the mixture composition where the UCST phase transition is detected. Finally, in line with an UCST scenario, our simulated membrane turns unstable at high temperature and alcohol concentration.

Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction.

The plasma membrane of eukaryotic cells is organized into lipid and protein microdomains, whose assembly mechanisms and functions are incompletely understood. We demonstrate that proteins in the nephrin/Nck/N-WASP actin-regulatory pathway cluster into micron-scale domains at the basal plasma membrane upon triggered phosphorylation of transmembrane protein nephrin. The domains are persistent but readily exchange components with their surroundings, and their formation is dependent on the number of Nck SH3 domains, suggesting they are phase separated polymers assembled through multivalent interactions among the three proteins. The domains form independent of the actin cytoskeleton, but acto-myosin contractility induces their rapid lateral movement. Nephrin phosphorylation induces larger clusters at the cell periphery, which are associated with extensive actin assembly and dense filopodia. Our studies illustrate how multivalent interactions between proteins at the plasma membrane can produce micron-scale organization of signaling molecules, and how the resulting clusters can both respond to and control the actin cytoskeleton.

Influence of Cyclodextrins on Thermosensitive and Fluorescent Properties of Pyrenyl-Containing PDMAA.

A series of pyrenyl-containing PDMAA copolymers were prepared by free radical copolymerization of dimethylacrylamide (DMAA) with pyrenebutanoyloxy ethyl methacrylate (PyBEMA). The structure of as-prepared copolymers was characterized by UV, FT-IR and 1H NMR spectroscopy. The effect of cyclodextrins (α-CD, β-CD and γ-CD) on the thermosensitivity and fluorescence of the copolymers in aqueous solutions were investigated. It was found that the as-prepared copolymers exhibit lower critical solution temperature (LCST)-type thermosensitivity. Cloud point (Tcp) decreases with the increasing molar content of PyBEMA unit in the copolymers. Tcp of the copolymers increases after the CD is added from half molar to equivalent amount relative to pyrenyl moiety, and that further adding twice equivalent CD results in a slight decrease in Tcp. The copolymers exhibit a pyrene emission located at 377 nm and a broad excimer emission centered at 470 nm. The copolymers in water present a stronger excimer emission (Intensity IE) relative to monomer emission (Intensity IM) than that in ethanol. The IE/IM values decrease after the addition of equivalent α-CD, β-CD and γ-CD into the copolymers in aqueous solution, respectively. The IE/IM values abruptly increase as the copolymers’ concentration is over 0.2 mg/L whether in ethanol solution or aqueous solution with or without CD, from which can probably be inferred that intra-polymeric pyrene aggregates dominate for solution concentration below 0.2 mg/L and inter-polymeric pyrene aggregates dominate over 0.2 mg/L. Furthermore, the formation of the CD pseudopolyrotaxanes makes it possible to form pyrene aggregates. For high concentration of 5 g/L, the copolymers and their inclusion complexes completely exhibit an excimer emission. The IE values abruptly increased as the temperature went up to Tcp, which indicates that the IE values can be used to research phase separation of polymers.

Polymerization Induced Phase Separation in Composite Latex Particles during Seeded Emulsion Polymerization

Multiphase structured latex particles have been studied and produced for decades; however, the mechanism governing the polymerization induced phase separation process in such particles remains incomplete. These particles are typically produced by starting with a first, single phase polymer particle dispersion, and then a second polymer, nearly always thermodynamically phase incompatible with the first, is polymerized within those seed particles. The Gibbs free energy change upon demixing is the driving force inducing polymer–polymer phase separation during polymerization (PIPS). However, the ultimate extent of phase separation is dictated by resistances to mutual polymer chain diffusion within the latex particles. Here, we have elucidated and quantified the contributions of thermodynamic driving force and kinetic diffusive limitations to polymer–polymer phase separation within composite nanoparticles. We present a means to evaluate both the influence of chemistry and process conditions on a master plot pr...

Organization of Chromatin by Intrinsic and Regulated Phase Separation

Eukaryotic chromatin is highly condensed but dynamically accessible to regulation and organized into subdomains. We demonstrate that reconstituted chromatin undergoes histone tail-driven liquid-liquid phase separation (LLPS) in physiologic salt and when microinjected into cell nuclei, producing dense and dynamic droplets. Linker histone H1 and internucleosome linker lengths shared across eukaryotes promote phase separation of chromatin, tune droplet properties, and coordinate to form condensates of consistent density in manners that parallel chromatin behavior in cells. Histone acetylation by p300 antagonizes chromatin phase separation, dissolving droplets invitro and decreasing droplet formation in nuclei. In the presence of multi-bromodomain proteins, such as BRD4, highly acetylated chromatin forms a new phase-separated state with droplets of distinct physical properties, which can be immiscible with unmodified chromatin droplets, mimicking nuclear chromatin subdomains. Our data suggest a framework, based on intrinsic phase separation of the chromatin polymer, for understanding the organization and regulation of eukaryotic genomes.

Directed Self-assembly of Vertical PS-b-PMMA Nanodomains Grown on Multilayered Polyelectrolyte Films

Layer-by-layer polyelectrolyte self-assembly, a common method for preparing high-quality ultra-thin films, was employed to direct the self-assembly behavior of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) block copolymer for the first time. Differing from the previous neutral polymer brushes anchored to silicon substrates via chemical modification, polyelectrolyte multilayers (PEMs) were anchored by electrostatic interaction and provided a stable, smooth, and neutral interface. In the present study, PS-b-PMMA was deposited on poly(acrylamide hydrochloride)/poly(acrylic acid) (PAH/PAA) PEMs prepared by layer-by-layer self-assembly to successfully yield vertical nanodomains after thermal annealing. Seven layered PEMs revealed an excellent, smooth surface, with a low roughness of 0.6 nm. The periodic structure with interlamellar spacing of 47 nm was determined by grazing-incidence small-angle X-ray scattering (GISAXS). The morphology of the PS-b-PMMA nanodomains depended on the polyanion-to-polycation concentration ratio, which is related to the interaction between the block copolymer and the substrate. Our results demonstrate that layer-by-layer self-assembly is a helpful method for the phase separation of block polymers and the fabrication of vertical, ordered nanodomains.

PMMA-LZO Composite Dielectric Film with an Improved Energy Storage Density

Energy storage materials in modern electronic devices and renewable energy systems are inevitable. The incorporation of inorganic fillers into the polymer matrix is a promising option for the advancement of storage materials with high energy density. The agglomeration of inorganic fillers in the polymer matrix and phase separation remain the main obstacles to efficient applications of the composites for energy storage. Here, the primary attention was given to achieve a uniform distribution of high-k LZO (Lanthanum Zirconium Oxide) filler into a PMMA (Polymethylmethacrylate) matrix to enhance the dielectric constant and energy storage density of PMMA while keeping dielectric loss at minimum. We prepared PMMA-LZO composite films with variable LZO content by ultrasound-assisted mixing followed by spin coating the solution on ITO (Indium tin oxide) coated glass. The effect of LZO content on dielectric properties of the LZO-PMMA films was studied. Dielectric constant (k) of PMMA was found to be increased from 3.1 to 15.3 at 15 vol.% LZO loading with a dielectric loss of 0.0582. However, 10 vol.% LZO loaded PMMA showed an improved dielectric constant of 13.4 while the dielectric loss remained the same as that of the neat PMMA. The LZO-PMMA films with 10 vol.% and 15 vol.% of LZO loading exhibited maximum energy density of 5.94 J cm−3 and 6.53 J cm−3, respectively. Overall, the 10 vol.% LZO loading was found to be optimum to achieve a stable film with improved dielectric properties. This work provides a viable approach for the development of flexible, high-energy density materials with a minimum dielectric loss.

Polymer Microspheres: Fabrication of Nanostructured Composite Microspheres Based on the Self‐Assembly of Polymers and Functional Nanomaterials (Part. Part. Syst. Charact. 9/2019)

In article number 1900178, Hiroshi Yabu reviews recent developments in the morphological control of microspheres based on the phase separation of polymers and the alignment control of functional nanoparticles inside the microspheres.

The Investigation of Flory-Huggins Interaction Parameters for Amorphous Solid Dispersion Across the Entire Temperature and Composition Range.

Amorphous solid dispersion (ASD) is one of the most promising enabling formulations featuring significant water solubility and bioavailability enhancements for biopharmaceutical classification system (BCS) class II and IV drugs. An accurate thermodynamic understanding of the ASD should be established for the ease of development of stable formulation with desired product performances. In this study, we report a first experimental approach combined with classic Flory–Huggins (F–H) modelling to understand the performances of ASD across the entire temperature and drug composition range. At low temperature and drug loading, water (moisture) was induced into the system to increase the mobility and accelerate the amorphous drug-amorphous polymer phase separation (AAPS). The binodal line indicating the boundary between one phase and AAPS of felodipine, PVPK15 and water ternary system was successfully measured, and the corresponding F–H interaction parameters (χ) for FD-PVPK15 binary system were derived. By combining dissolution/melting depression with AAPS approach, the relationship between temperature and drug loading with χ (Φ, T) for FD-PVPK15 system was modelled across the entire range as χ = 1.72 − 852/T + 5.17·Φ − 7.85·Φ2. This empirical equation can provide better understanding and prediction for the miscibility and stability of drug-polymer ASD at all conditions.

Fabrication of Nanostructured Composite Microspheres Based on the Self‐Assembly of Polymers and Functional Nanomaterials

AbstractThis Review examines recent developments in the morphological control of polymer microspheres fabricated via the phase separation of polymers as well as the alignment of functional nanoparticles inside microspheres prepared by so‐called bottom‐up synthesis techniques. Several methods for adjusting the internal and surface morphologies of polymer microspheres based on the phase separation of polymer blends and block copolymers are discussed, and the effects of microsphere size on phase separated structures and theoretical simulations of morphologies are also reviewed. The alignment of functional nanoparticles in phase separated polymer microspheres and applications of nanostructured and hybrid polymer microspheres are summarized.

Outcoupling-enhanced organic light-emitting diodes using simple phase-separated polymer films

A high-performance external light outcoupling film for organic light-emitting diodes (OLEDs) is developed using a novel phase-separated polymer (PSP) which is spontaneously formed from a homogeneous solution of poly(amic acid) and polyimide in dimethylacetamide. The phase separation during the spin-coating process leads to complex morphologies of film with random microdent and nanobump patterns by a self-assembly of polymers. The PSP film is utilized on the backside of a glass substrate in green OLEDs as a light outcoupling film, leading to a considerable enhancement of light outcoupling efficiency. Both the current efficiency and power efficiency of OLEDs with the PSP film are improved by a factor of 1.45 and 1.53, respectively, in comparison with those of the reference device. The results demonstrate that the PSP film could serve as a promising outcoupling film for OLEDs.

Conservation-Dissipation Formalism for soft matter physics: I. Augmentation to Doi's variational approach

In the first paper of this series, we prove that by choosing the proper variational function and variables, the variational approach proposed by Doi in soft matter physics is equivalent to the Conservation-Dissipation Formalism. To illustrate the correspondence between these two theories, several novel examples in soft matter physics, including the particle diffusion in dilute solutions, polymer phase separation dynamics and nematic liquid crystal flows, are carefully examined. Based on our work, a deep connection among the generalized Gibbs relation, the second law of thermodynamics and the variational principle in non-equilibrium thermodynamics is revealed.