Tailoring Multiphasic Protein Condensates via Liquid‐Liquid Phase Separation

The effects of an electric field on upper critical solution temperature (UCST) phase separation and crystallization behavior in binary blends of poly(vinylidene fluoride) (PVDF) and poly(methyl methacrylate) (PMMA) were investigated by means of time-resolved small-angle light scattering (SALS) and polarizing optical microscopy (POM). The lower critical solution temperature (LCST) phase separation curve of this blend could not be measured experimentally due to thermal decomposition caused by too high LCSTs. However, the UCST-type phase separation curve was observed from SALS measurements to shift toward higher temperatures under the electric field. In the temperature range above the UCST (150 °C ≤ T ≤ 158 °C), the electric field reduces the overall crystallization rate in the neat PVDF and, in contrast, increases the crystallization rate in 95/5, 90/10, and 85/15 PVDF/PMMA blends. In the temperature range below the UCST (130 °C ≤ T ≤ 143 °C), the electric field also increased the overall crystallization rate in the 80/20 and 70/30 PVDF/PMMA blends. POM images were also used to investigate the effect of the electric field on the overall melt-crystallization rate, nucleation rate, and crystalline morphology in PVDF/PMMA blends.

Core-shell microgels were synthesized via a free radical emulsion polymerization of thermoresponsive poly-(N-isopropyl acrylamide), pNipam, on the surface of silica nanoparticles. Pure pNipam microgels have a lower critical solution temperature (LCST) of about 32 °C. The LCST varies slightly with the crosslinker density used to stabilize the gel network. Including a silica core enhances the mechanical robustness. Here we show that by varying the concentration gradient of the crosslinker, the thermoresponsive behaviour of the core-shell microgels can be tuned. Three different temperature scenarios have been detected. First, the usual behaviour with a decrease in microgel size with increasing temperature exhibiting an LCST; second, an increase in microgel size with increasing temperature that resembles an upper critical solution temperature (UCST), and; third, a decrease with a subsequent increase of size reminiscent of the presence of both an LCST, and a UCST. However, since the chemical structure has not been changed, the LCST should only change slightly. Therefore we demonstrate how to tune the particle size independently of the LCST.

Development of high flux ultrafiltration polyphenylsulfone membranes applying the systems with upper and lower critical solution temperatures: Effect of polyethylene glycol molecular weight and coagulation bath temperature

ABSTRACTHydrophilic biocompatible surfaces can be obtained by grafting stimuli‐sensitive polymers onto commercially available medical devices. Thermo and pH‐responsive polymers are two of the most studied materials due to their potential application as drug delivery systems. Poly(N‐vinylcaprolactam) has a lower critical solution temperature (LCST) near to physiological temperature. However, when it is grafted with pH‐sensitive moieties its LCST it is affected undergoing remarkable displacements. We studied the effect of acrylic acid (AAc), 4‐vinylpyridine (4VP), and 1‐vinylimidazole (Vim) on the LCST of N‐vinylcaprolactam (NVCL) grafted onto silicone rubber (SR), and SR‐g‐NVCL (32.5 °C). The binary graft copolymers were obtained by ionizing grafting radiation using the simultaneous technique; the samples were characterized by Fourier transform infrared attenuated total reflectance (FTIR‐ATR), cross‐polarization magic angle spinning nuclear magnetic resonance (CP/MAS 13C‐NMR), and thermogravimetrical analysis (TGA). LCST value was dramatically affected by the comonomer content; even it was observed the switching from LCST to upper critical solution temperature (UCST) for (SR‐g‐NVCL)‐g‐AAc and (SR‐g‐NVCL)‐g‐4VP samples. The observed behavior is rarely reported for binary graft copolymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48170.

We rationally designed a monomer that when polymerized formed a well-defined nonionic polymer [poly(2-(methacryloyloxy) ethylureido glycinamide), PMEGA] by reversible addition fragmentation chain transfer with a flat and tunable upper critical solution temperature (UCST) in water. The monomer was made in one pot from commercially available compounds and with ease of purification. Strong hydrogen-bonding side groups on the polymer produced sharp coil-to-globule transitions upon cooling below its UCST. Ideal random copolymers produced with butyl methacrylate also showed flat UCST profiles, in which the UCST increased with a greater butyl methacrylate copolymer composition from 7 to 65 °C. In the presence of NaCl, the UCST decreased linearly with NaCl concentration due to the "salting-in" effect, and it was found that the slopes from the linear decrease of UCST were nearly identical for all copolymer compositions. This new polymer and its copolymers support the hypothesis that strong hydrogen bonding between the side groups allowed the flat UCST to be readily tuned with a high level of predictability. We postulate that this polymer system may provide wide biological applicability similar to that found for the well-used flat lower critical solution temperature (LCST) of poly(N-isopropylacrylamide).

A novel monomer, N‐(2‐((3‐morpholine‐3‐isopropyl)thio)ethyl)methacrylamide (MTMA), is synthesized and polymerized by reversible addition‐fragmentation chain transfer (RAFT) polymerization to give a thermoresponsive polymer poly[N‐(2‐((3‐morpholino‐3‐oxopropyl)thio)ethyl)methacrylamide] (PMTMA). PMTMA exhibits reversible thermoresponsive phase transitions of the lower critical solution temperature (LCST) type in water and the upper critical solution temperature (UCST) type in ethanol and methanol. The degree of polymerization and concentration of PMTMA, and solvent type have a significant influence on the transition temperature. PMTMA shows complicated thermoresponse in water–alcohol mixtures. In water–ethanol mixtures, the phase diagram of PMTMA can be divided into three regions according to ethanol volume percentages, φ: 0 ≤ φ < 15% for an LCST region; 15% ≤ φ < 91.5% for a complete dissolution region; 91.5% ≤ φ ≤ 100% for a UCST region. At high water content, the LCST increases with increasing ethanol content; and at high ethanol content, the UCST decreases with increasing water content. In water–methanol mixtures, PMTMA shows more complex thermoresponse. In the range of 0–50 °C, the phase diagram can be divided into five regions, depending on the methanol volume percentages φ: 0 ≤ φ < 15% for LCST region; 15% ≤ φ < 25% for immiscible region; 25% ≤ φ < 85% for UCST region; 85% ≤ φ < 95% for fully dissolved region; 95% ≤ φ ≤ 100% for another UCST region.

The kinetics of water transfer between the lower critical solution temperature (LCST) and upper critical solution temperature (UCST) thermoresponsive blocks in about 10 nm thin films of a diblock copolymer is monitored by in situ neutron reflectivity. The UCST‐exhibiting block in the copolymer consists of the zwitterionic poly(4‐((3‐methacrylamidopropyl)dimethylammonio)butane‐1‐sulfonate), abbreviated as PSBP. The LCST‐exhibiting block consists of the nonionic poly(N‐isopropylacrylamide), abbreviated as PNIPAM. The as‐prepared PSBP80‐b‐PNIPAM400 films feature a three‐layer structure, i.e., PNIPAM, mixed PNIPAM and PSBP, and PSBP. Both blocks have similar transition temperatures (TTs), namely around 32 °C for PNIPAM, and around 35 °C for PSBP, and with a two‐step heating protocol (20 °C to 40 °C and 40 °C to 80 °C), both TTs are passed. The response to such a thermal stimulus turns out to be complex. Besides a three‐step process (shrinkage, rearrangement, and reswelling), a continuous transfer of D2O from the PNIPAM to the PSBP block is observed. Due to the existence of both, LCST and UCST blocks in the PSBP80‐b‐PNIPAM400 film, the water transfer from the contracting PNIPAM, and mixed layers to the expanding PSBP layer occurs. Thus, the hydration kinetics and thermal response differ markedly from a thermoresponsive polymer film with a single LCST transition.

A new family of the thermo-responsive polymers based on poly[N-(4-vinylbenzyl)-N,N-dialkylamine] with the pendent amine group as well as the doubly thermo-responsive triblock copolymer were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. These polymers showed the lower critical solution temperature (LCST) and/or the upper critical solution temperature (UCST) in alcohol and in the alcohol/water mixture. The polymer molecular weight, the polymer concentration, the cosolvent/nonsolvent and the deuterated solvent affecting the LCST and/or UCST were investigated, and their great influence on the LCST/UCST was demonstrated. The origin of the phase transition of poly[N-(4-vinylbenzyl)-N,N-dialkylamine] at LCST upon heating was investigated and the possible reason was proposed. The doubly thermo-responsive triblock copolymer of PVMA53-b-PVEA108-b-PVMA53 underwent phase transition at two LCST temperatures. The PVEA108 block underwent the initial phase transition at the first LCST of 32.5 °C to form core–corona micelles, and then the subsequent phase transition of the PVMA53 block took place at the second LCST of 54.5 °C to produce corona-collapsed micelles. The proposed polymers based on poly[N-(4-vinylbenzyl)-N,N-dialkylamine] are anticipated to broaden the thermo-responsive polymer range and will be useful in polymer science.

This section pertains to the implementation of emulsion polymerization of MMA in n-Heptane under conventional precipitation environment (as low as 60°C reactor operating temperature), although there is the likelihood that emulsion particles react at temperature above the lower critical solution temperature (LCST). Even though phase separation below the upper critical solution temperature (UCST) is believed to occur at the start of reaction within emulsion particles, the hour-glass phase envelope of the PMMA–MMA–n-Heptane system has been shown to provide a pathway system temperature to attain higher levels where they could well go above the LCST. The polymerization system is based on a redox initiation formulation, and the formation of block copolymer in emulsion particles is implemented in a two-stage polymerization procedure. Solvent/precipitant is removed through a stripping operation. In order to minimize residual monomer in the system at the end of the two-stage reaction run and solvent/precipitant removal step, a chase initiator solution is admixed into the reactor. Product emulsion is used as a binder for a latex paint formulation, which is applied as a film and tested for various coating properties.

"Schizophrenic" diblock copolymers containing nonionic and zwitterionic blocks were prepared with well-controlled molecular weights via atom-transfer radical polymerization (ATRP). In this work, we report a systematic study of how morphological changes of poly(N-isopropylacrylamide)-block-poly(sulfobetaine methacrylate) (PNIPAAm-b-PSBMA) copolymers affect hemocompatibility in human blood solution. The "schizophrenic" behavior of PNIPAAm-b-PSBMA was observed by (1)H NMR, dynamic light scattering (DLS), and turbidity measurement with double morphological transition, exhibiting both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in aqueous solution. Below the UCST of PSBMA block, micelles were obtained with a core of insoluble PSBMA association and a shell of soluble PNIPAAm, whereas the opposite micelle structure was observed above the LCST of PNIPAAm block. In between the UCST and LCST, unimers with both soluble blocks were detected. Hydrodynamic size of prepared polymers and copolymers is determined to illustrate the correlations between intermolecular nonionic/zwitterionic associations and blood compatibility of PNIPAAm, PNIPAAm-b-PSBMA, and PSBMA suspension in human blood. Human fibrinogen adsorption onto the PNIPAAm-b-PSBMA copolymers from single-protein solutions was measured by DLS to determine the nonfouling stability of copolymer suspension. The new nonfouling nature of PNIPAAm-b-PSBMA copolymers was demonstrated to show extremely high anticoagulant activity and antihemolytic activity in human blood over a wide range of explored temperatures from 4 to 40 °C. The temperature-independent blood compatibility of nonionic/zwitterionic block copolymer along with their schizophrenic phase behavior in aqueous solution suggests their potential in blood-contacting applications.

Effects of polydispersity on liquid–liquid equilibrium of polymeric fluids

versatile [1]. In recent years, polymer-micellar systems have been designed that are adaptable to their environment and able to respond in a controlled manner to external stimuli. In short, synthesis of 'nanoscale objects' that exhibit 'stimulus-responsive' properties is a topic gathering momentum, because their behavior is reminiscent of that exhibited by proteins [8]. By integrating environmentally sensitive homopolymers into amphiphilic block copolymers, smart block copolymers with self assembled supramolecular structures that exhibit stimuli or environmentally responsive properties can be obtained [1]. Several synthetic polymers are known to have environmentally responsive properties. Changes in the physical, chemical or biochemical environment of these polymers results in modulation of the solubility or chain conformation of the polymer [9]. There are many common schemes of engineering stimuli responsive properties into materials [8, 9]. Polymers exhibiting lower critical solution temperature (LCST) are soluble in solvent below a specific temperature and phase separate from solvent above that temperature while polymers exhibiting upper critical solution temperatures (UCST) phase separate below a certain temperature. The solubility of polymers with ionizable moieties depends on the pH of the solution. Polymers with polyzwitterions, anions and cations have been shown to exhibit pH responsive self assembly. Other stimuli responsive polymers include glucose sensitive polymers, calcium ion-sensitive polymers and so on. Progress in living radical polymerization (LRP) methods [10] has made it possible for the facile synthesis of these block copolymer systems with controlled molecular weights and well defined architectures. The overall theme of this work is to develop novel smart block copolymers for biomineralization and biomedical applications. Synthesis and characterization of self-assembling thermoreversible ionic block copolymers as templates in biomimetic nanocomposite synthesis using a bottom-up approach is a novel contribution in this respect. Further, we have extended these families of copolymers to include block copolymer-peptide conjugates to enhance biological specificity. Future directions on this work will focus on enhancing the polymer templating properties for biomineralization by expanding the family of block copolymers with organic polypeptides and biological polypeptide scaffolds as well as a detailed understanding of the polymer-inorganic nanocomposites at the molecular level using small angle scattering analysis. Glucose responsive polymer hydrogels for drug delivery, polymer-ligand conjugates for non-viral therapy and thermoresponsive injectable photocrosslinkable hydrogels for posttraumatic arthritis cartilage healing are other applications of these novel copolymers synthesized in our work.

Smart windows are effective in reducing the energy consumption of air conditioning and lighting systems, while contributing to maintaining the comfort zone of temperature in the indoor environment. Currently used smart windows mainly rely on traditional single-phase thermochromic material in which only one abrupt optical change occurs during temperature changes, and their inherent characteristics may not be suited for a practical balance of energy saving and privacy protection. Here, we developed a novel bidirectional optically responsive smart window (BSW) with unique bidirectional optical response features by introducing sodium dodecyl sulfate (SDS)/potassium tartrate (PTH) micelles into PNIPAM hydrogel to form a composite hydrogel, which was encapsulated in two glass panels. The upper critical solution temperature (UCST) and lowest critical solution temperature (LCST) of the material can be individually adjusted and are capable of matching the human comfort zone of temperature. In addition, the smart window exhibits remarkable transparency (92.5%), visible light transmission ratio (Tlum = 91.31%), and excellent solar modulation (ΔTsol,UCST = 76.34%, ΔTsol,LCST = 76.75%). Moreover, it possesses selectivity in transmitting light in the infrared band of solar radiation and can complete the "transparent-opaque" transition in a very narrow temperature range (<1 °C). When at comfortable temperatures, the highly transparent smart windows facilitate interior light and appreciation of the view. At low temperatures, SDS/PTH micelles aggregate to form large micelles, blocking the transmission of light and protecting customer privacy. At high temperatures, PNIPAM can undergo a "sol-gel" transition, thus blocking incident solar radiation. Taken together, these proposed materials with bidirectional optical response characteristics would be harnessed as a promising platform for building energy conservation, anti-counterfeiting, information encryption, and temperature monitoring.

Crystalline colloidal arrays (CCAs) composed of core-shell microspheres with thermoresponsive structural iridescence governed by Bragg's law have garnered significant attention for diverse applications. While core-shell microspheres with lower critical solution temperature (LCST) properties are extensively studied, upper critical solution temperature (UCST) counterparts remain unexplored, offering the potential to expand the application scope of thermoresponsive CCAs. In this study, poly(N-acryloyl glycinamide) (PNAGA), a UCST homopolymer, is employed for the first time to synthesize core-shell microspheres. By copolymerizing NAGA with the hydrophilic co-monomer acrylamide (AM) to form the shell, microspheres with soft shells capable of assembling into CCAs with bright iridescence are obtained. Owing to Bragg's law and the UCST properties of the shell, the diffraction wavelength of these CCAs depends on concentration, observation angle, and temperature. The CCAs exhibit thermoresponsive behavior, with a size transition temperature around 14°C. Upon heating, the shells swell, and the microspheres transition from a rigid to a soft state, leading to an increase in interparticle distance and enhanced stabilization of the ordered microsphere packing. This process results in a red shift and a significant increase in the intensity of the diffraction peak. The thermoresponsive properties of these CCAs highlight their potential as intelligent temperature-sensing materials.

Co-solvent concentration influence of two- and three-component systems on the high pressure cloud-point behavior for the poly(vinyl stearate) under supercritical CO2