Morphological Transition Research Articles

Crystallographic faceting of bulk tungsten surfaces observed during in situ heating in an environmental scanning electron microscope

The surface faceting of metals has been studied for several decades, typically using experimental methods such as low-energy electron diffraction. In the current paper, surface faceting of tungsten pellets was studied during in situ heating inside an environmental scanning electron microscope (ESEM), which allowed for direct, high-fidelity observation of morphological changes in response to high-temperature annealing under a moderate vacuum (0.8 Torr). Additionally, a second set of tungsten samples was annealed in an ultrahigh vacuum chamber (10−8 Torr), albeit without direct observation via ESEM. This study revealed that oxygen plays a crucial role in tungsten surface faceting and in a morphological transition to vertex rounding. Furthermore, this paper discusses relevant techniques for identifying the crystallographic indices of surface facets. It is demonstrated that a combination of electron backscatter diffraction, tilted-sample imaging from multiple angles, and serial sectioning in a focused ion beam system can be effectively deployed to determine the geometry of faceting, which in turn can be verified with the aid of software for generating Wulff shapes. The influence of processing environment on tungsten surface faceting enables the possibility of designing and controlling the morphology and crystallographic facets of tungsten surfaces.

Epitaxial AlN film with improved quality on Si (111) substrates realized by boron pretreatment via MOCVD

This study investigated the growth of AlN epitaxial films on 2-in. Si(111) via metal-organic chemical vapor deposition. By introducing triethylboron (TEB) during trimethylaluminum pretreatment, a nearly crack free AlN epilayer with a thickness of 500 nm was acquired. The x-ray diffraction rocking curves of AlN (002) and (102) exhibited full width at half maximum values of 0.22° and 0.36°, respectively. Atomic force microscopy image analysis showed that after the introduction of TEB, larger grains appeared on the surface of Si(111) substrate, promoting the 3D growth pattern of the subsequent AlN buffer layer. Laytec reflection curves depicted the morphological transition from 3D to 2D growth mode during AlN deposition. At the same time, the curvature value was significantly reduced by 20 km−1, and the Raman spectrum peak of E2(high) shifted from 648.7 to 652.5 cm−1, indicating that the surface tensile stress was greatly reduced, effectively suppressing the crack problem of AlN on Si(111).

Structural and Morphological Studies of Pt in the As-Grown and Encapsulated States and Dependency on Film Thickness.

The morphology and crystal structure of Pt films grown by pulsed laser deposition (PLD) on yttria-stabilized zirconia (YSZ)at high temperatures Tg = 900 °C was studied for four different film thicknesses varying between 10 and 70 nm. During the subsequent growth of the capping layer, the thermal stability of the Pt was strongly influenced by the Pt film's thickness. Furthermore, these later affected the film morphology, the crystal structure and hillocks size, and distribution during subsequent growth at Tg = 900 °C for a long duration. The modifications in the morphology as well as in the structure of the Pt film without a capping layer, named also as the as-grown and encapsulated layers in the bilayer system, were examined by a combination of microscopic and scattering methods. The increase in the thickness of the deposited Pt film brought three competitive phenomena into occurrence, such as 3D-2D morphological transition, dewetting, and hillock formation. The degree of coverage, film continuity, and the crystal quality of the Pt film were significantly improved by increasing the deposition time. An optimum Pt film thickness of 70 nm was found to be suitable for obtaining a hillock-free Pt bottom electrode which also withstood the dewetting phenomena revealed during the subsequent growth of capping layers. This achievement is crucial for the deposition of functional bottom electrodes in ferroelectric and multiferroic heterostructure systems.

A novel and ubiquitous miRNA-involved regulatory module ensures precise phosphorylation of RNA polymerase II and proper transcription.

Proper transcription orchestrated by RNA polymerase II (RNPII) is crucial for cellular development, which is rely on the phosphorylation state of RNPII's carboxyl-terminal domain (CTD). Sporangia, developed from mycelia, are essential for the destructive oomycetes Phytophthora, remarkable transcriptional changes are observed during the morphological transition. However, how these changes are rapidly triggered and their relationship with the versatile RNPII-CTD phosphorylation remain enigmatic. Herein, we found that Phytophthora capsici undergone an elevation of Ser5-phosphorylation in its uncanonical heptapeptide repeats of RNPII-CTD during sporangia development, which subsequently changed the chromosomal occupation of RNPII and primarily activated transcription of certain genes. A cyclin-dependent kinase, PcCDK7, was highly induced and phosphorylated RNPII-CTD during this morphological transition. Mechanistically, a novel DCL1-dependent microRNA, pcamiR1, was found to be a feedback modulator for the precise phosphorylation of RNPII-CTD by complexing with PcAGO1 and regulating the accumulation of PcCDK7. Moreover, this study revealed that the pcamiR1-CDK7-RNPII regulatory module is evolutionarily conserved and the impairment of the balance between pcamiR1 and PcCDK7 could efficiently reduce growth and virulence of P. capsici. Collectively, this study uncovers a novel and evolutionary conserved mechanism of transcription regulation which could facilitate correct development and identifies pcamiR1 as a promising target for disease control.

Observation of an abrupt 3D-2D morphological transition in thin Al layers grown by MBE on InGaAs surface

Among superconductor/semiconductor hybrid structures, in situ aluminum (Al) grown on InGaAs/InAs is widely pursued for the experimental realization of Majorana Zero Mode quasiparticles. This is due to the high carrier mobility, low effective mass, and large Landé g-factor of InAs, coupled with the relatively high value of the in-plane critical magnetic field in thin Al films. However, growing a thin, continuous Al layer using the molecular beam epitaxy (MBE) is challenging due to aluminum's high surface mobility and tendency for 3D nucleation on semiconductor surfaces. A study of epitaxial Al thin film growth on In0.75Ga0.25As with MBE is presented, focusing on the effects of the Al growth rate and substrate temperature on the nucleation of Al layers. We find that for low deposition rates, 0.1 and 0.5 Å/s, the growth continues in 3D mode during the deposition of the nominal 100 Å of Al, resulting in isolated Al islands. However, for growth rates of 1.5 Å/s and above, the 3D growth mode quickly transitions into island coalescence, leading to a uniform 2D Al layer. Moreover, this transition is very abrupt, happening over an Al flux increase of less than 1%. We discuss the growth mechanisms explaining these observations. The results give new insights into the kinetics of Al deposition and show that with sufficiently high Al flux, a 2D growth on substrates at close to room temperature can be achieved already within the first few Al monolayers. This eliminates the need for complex cryogenic substrate cooling and paves the way for the development of high-quality superconductor-semiconductor interfaces in standard MBE systems.

Convoluted micellar morphological transitions driven by tailorable mesogenic ordering effect from discotic mesogen-containing block copolymer

Solution-state self-assemblies of block copolymers to form nanostructures are tremendously attractive for their tailorable morphologies and functionalities. While incorporating moieties with strong ordering effects may introduce highly orientational control over the molecular packing and dictate assembly behaviors, subtle and delicate driving forces can yield slower kinetics to reveal manifold metastable morphologies. Herein, we report the unusually convoluted self-assembly behaviors of a liquid crystalline block copolymer bearing triphenylene discotic mesogens. They undergo unusual multiple morphological transitions spontaneously, driven by their intrinsic subtle liquid crystalline ordering effect. Meanwhile, liquid crystalline orderedness can also be built very quickly by doping the mesogens with small-molecule dopants, and the morphological transitions are dramatically accelerated and various exotic micelles are produced. Surprisingly, with high doping levels, the self-assembly mechanism of this block copolymer is completely changed from intramolecular chain shuffling and rearrangement to nucleation-growth mode, based on which self-seeding experiments can be conducted to produce highly uniform fibrils.

Effect of solution treatment on the microstructure, phase transformation behavior and functional properties of NiTiNb ternary shape memory alloys fabricated via laser powder bed fusion in-situ alloying

Post-heat treatment is commonly employed to improve the microstructural homogeneity and enhance the mechanical performances of the additively manufactured metallic materials. In this work, a ternary (NiTi)91Nb9 (at.%) shape memory alloy was produced by laser powder bed fusion (L-PBF) using pre-alloyed NiTi and elemental Nb powders. The effect of solution treatment on the microstructure, phase transformation behavior and mechanical/functional performances was investigated. The in-situ alloyed (NiTi)91Nb9 alloy exhibits a submicron cellular-dendritic structure surrounding the supersaturated B2-NiTi matrix. Upon high-temperature (1273 K) solution treatment, Nb-rich precipitates were precipitated from the supersaturated matrix. The fragmentation and spheroidization of the NiTi/Nb eutectics occurred during solution treatment, leading to a morphological transition from mesh-like into rod-like and sphere-like. Coarsening of the β-Nb phases occurred with increasing holding time. The martensite transformation temperature increases after solution treatment, mainly attributed to: (i) reduced lattice distortion due to the Nb expulsion from the supersaturated B2-NiTi, and (ii) the Ti expulsion from the β-Nb phases that lowers the ratio Ni/Ti in the B2-NiTi matrix, which resulted from the microstructure changes from non-equilibrium to equilibrium state. The thermal hysteresis of the solutionized alloys is around 145 K after 20% pre-deformation, which is comparable to the conventional NiTiNb alloys. A short-term solution treatment (i.e. at 1 273 K for 30 min) enhances the ductility and strength of the as-printed specimen, with the increase of fracture stress from (613 ± 19) MPa to (781 ± 20) MPa and the increase of fracture strain from (7.6 ± 0.1)% to (9.5 ± 0.4)%. Both the as-printed and solutionized samples exhibit good tensile shape memory effects with recovery rates >90%. This work suggests that post-process heat treatment is essential to optimize the microstructure and improve the mechanical performances of the L-PBF in-situ alloyed parts.

Synthesis and characterization of Co3O4 spinel nanowall: understanding the growth mechanism and properties

Formation of spinel tricobalt tetraoxide (Co3O4) nanostructures through a controlled thermal oxidation process is discussed here. Thin films of high purity cobalt (Co) were deposited on glass/quartz substrates using an electron beam (E-beam) evaporation technique. Thermal oxidation of the as-deposited Co thin films was carried out at various oxidation temperatures (400 °C to 600 °C) for different durations (5 h to 15 h) to grow various oxide nanostructures. Different surface characterizations techniques were used to investigate the structure, chemistry and electronic properties of the as-grown cobalt oxide nanostructures. x-ray diffraction analysis revealed the presence of the CoO phase along with the Co3O4 phases at relatively lower oxidation temperature. However, the Co3O4 phase becomes more predominant for longer oxidation durations at higher oxidation temperatures. Field emission scanning electron microscopy analysis showed a surface morphological transition from nanowalls to nanograins with an increase in the oxidation temperature. The surface electrical conductivity of the oxidized Co films is also increased for higher oxidation temperature and/or duration mainly due to the oxide phase purity and larger particle sizes. Ultraviolet–visible spectroscopy indicated two distinct optical energy bandgaps, which effectively decreased with an increase in the oxidation temperature and duration. Raman spectroscopy identified five different Raman-active modes corresponding to the Co3O4 phase, with the F2g mode dominating at higher temperatures. All these findings provide clear insights into the structural, electrical, chemical and optical properties of cobalt oxide thin films. Moreover, it provides a mechanism on how to grow 2D nanowalls morphology of Co3O4 films which can further be used in energy, sensor or catalytic applications.

Influence of Polymer Side Chain Size and Backbone Length on the Self-Assembly of Supramolecular Polymer Bottlebrushes.

Hydrogen bonds are a versatile tool for creating fibrous, bottlebrush-like assemblies of polymeric building blocks. However, a delicate balance of forces exists between the steric repulsion of the polymer chains and these directed supramolecular forces. In this work we have systematically investigated the influence of structural parameters of the attached polymers on the assembly behaviour of benzene trisurea (BTU) and benzene tris(phenylalanine) (BTP) conjugates in water. Polymers with increasing main chain lengths and different side chain sizes were prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization of hydroxyethyl acrylate (HEA), tri(ethylene glycol) methyl ether acrylate (TEGA) and oligo(ethylene glycol) methyl ether acrylate (OEGA). The resulting structures were analyzed using small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Both BTU and BTP formed fibres with PHEA attached, but a transition to spherical morphologies was observed at degrees of polymerisation (DP) of 70 and above. Overall, the main chain length appeared to be a dominating factor in inducing morphology transitions. Increasing the side chain size generally had a similar effect but mainly impeded any aggregation as is the case of POEGA. Interestingly, BTP conjugates still formed fibres, suggesting that the stronger intermolecular interactions can compensate partially for the steric repulsion.

Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress.

Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 μg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.

Ultrasonic cavitation-modulated nanocrystal facets growth of zinc-based oxide

In this study, in situ detection of the transient cavitation intensity during the sonochemical synthesis of Zinc-based Oxide (ZBO) is realized. At a fixed ethanol/water ratio of 25%, the transient cavitation intensity initially increases to a certain level during the nucleation stage of ZBO since the growth units of ZBO serve as supplementary induction sites for transient cavitation bubbles. Once the process surpasses the critical supersaturation point of ZBO growth units, a decrease of transient cavitation intensity is observed because the formation of massive ZBO nanocrystals may cause ultrasonic scattering attention. As a result, high-aspect-ratio ZBO nanorods are formed due to the preferential growth along the [001] direction. In addition, by increasing the ethanol/water ratio, a similar but decreasing trend in the time-dependent transient cavitation intensity during the ZBO synthesis process is obtained. This results in fewer ethanol molecules detaching from the ZBO (001) crystal surface, due to reduced cavitation bubble explosions, thereby inhibiting ZBO growth along the [001] direction. At an ethanol/water ratio of 75%, a morphological transition from slender nanorods to ultra-thin Zn5(NO3)2(OH)8·2H2O nanoflakes is facilitated. These ultra-thin nanoflakes demonstrate promising photocatalytic performance. This work provides a rational sonochemical approach for synthesizing facet-controlled growth of nanocrystals.

Semi-Solid Slurries for Rheocasting of Hypoeutectic Al-Si-X Alloys Produced by Self-Stirring in Serpentine Channels

Nowadays it is common to see the production of complex and critical automotive and aeronautical components reduced in weight for energy efficiency using light alloys with improved microstructural and mechanical properties. The casting processes involved in this trend are strong; in this study, an optimized design of a vertical serpentine channel and a novel design of a horizontal serpentine channel to produce semi-solid slurry (S2S) with thixotropic behavior by self-stirring for rheocasting of A380 and A356 alloys are tested. Simultaneously, chilling during solidification, flow development, and shearing on the alloys to improve the performance of solid fractions and self-stirring at high shear rate are applied. The effects of these conditions on the modification of the morphology transition of the α(Al) phase from dendrite to equiaxed grain are discussed. The results suggest the ability of the mentioned processes to promote the morphological transition of the primary solid due to the produced equiaxed grains of α(Al) phase having sizes between 25–50 µm from A380 alloy processed by vertical self-stirring. On the other hand, the treatment of the A356 alloy using the new horizontal serpentine channel produces equiaxed grains with an average size of 39 µm. Unexpected Si crystals, trapped in the α(Al) phase using both methods with both alloys, are detected. The applied operation parameters were aided by gravity-pouring close to the liquidus temperature, and the obtained microstructural results show the ability for S2S to form alongside thixotropic behavior and non-dendritic solidification by mean of self-stirring in the serpentine channels, suggesting the potential for further experiments under die-casting conditions.

Deposition of high-quality, nanoscale SiO2 films and 3D structures

Silicon dioxide (SiO2) is ubiquitous in biomedical diagnostics and other applications as a capture medium for nucleic acids and proteins. Diagnostic devices have seen rapid miniaturisation in recent years, due to the increased demand for portable point-of-care diagnostics. However, there are increasing challenges with incorporating SiO2 nanostructures into diagnostic devices, due to the complexity of nanostructured SiO2 synthesis, often involving etching and chemical vapour deposition under high vacuum conditions.We report a novel and straightforward method for deposition of high-quality, nanoscale SiO2 films and 3D SiO2 structures using thermal decomposition of polydimethylsiloxane (PDMS), in a furnace at atmospheric pressure at 500 °C. This method allows individual nanometre controllability of conformal pinhole-free layers on a variety of materials and morphologies. The temperature ramp rate is a key factor in determining the SiO2 deposit morphology, with slower ramp rates leading to highly conformal 2D films and faster ones yielding 3D nanodentrite structures. For the 2D films, the film thickness, as determined by spectroscopic ellipsometry and confirmed by SEM data, is shown to correlate excellently with initial PDMS source material mass in the thickness range 0.8–18 nm. Fits to ellipsometry models confirm that the refractive index of the deposited film matches the expected value for SiO2, while electrical breakdown measurements confirm that the breakdown strength of the films is comparable to that of high-quality thermal oxides. Depositions on high aspect ratio ZnO nanostructures are shown to be highly conformal, leading to core-shell ZnO-SiO2 nanostructures whose shell thickness is in excellent agreement with the expected values from deposition on planar substrates. At faster ramp rates an abrupt morphological transition is seen to a deposit which displays a 3D nanodentrite morphology. The possibilities for applications of both morphologies (and core-shell combinations with other nanostructured materials) in biosensing and related areas are briefly discussed, and the DNA capture capabilities of each nanostructure are measured. The high aspect ratio nanodendrite structures allow for significant DNA capture within microfluidic devices in the presence of low DNA concentrations, with a maximum average capture efficiency of 43.4 % achieved in the presence of 10 ng/mL of DNA, which is an improvement by a factor of ∼ 3 over planar Si surfaces. Improvements by factors of >10 over planar surfaces were achieved at higher DNA concentrations of 100 and 1000 ng/mL.

Effects of DC bias on evolutions of repetitively pulsed streamer discharge in humid air

Modulation efficiency and mechanisms of repetitively pulsed streamer discharge in humid air are ambiguous with dramatic variations in free electron availability, residual ion mobility, enhanced heat release, etc, caused by water molecules intentionally supplemented or existing in the surrounding environment. The inception and propagation patterns of repetitively pulsed streamer discharge modulated by superimposed DC bias are experimentally investigated in the needle-plane electrode configuration. The inception voltage decreases due to negative ion drift under positive DC bias. The secondary streamer with a bright glowing cloud prolongs towards the plane electrode and the diameter decreases under positive DC bias. The primary streamer tends to propagate along the off-axis direction under negative DC bias. The number of applied pulses before breakdown decreases with the increase in positive DC bias and illustrates an insignificant dependence on the negative DC bias. The effect of air humidity is more pronounced than the DC bias. The streamer inception, propagation, and morphological transition are explained by residual space charge distributions and drift velocity.

Morphology Transitions of SDS Coatings on Single-Walled Carbon Nanotubes

Morphology Transitions of SDS Coatings on Single-Walled Carbon Nanotubes

Multifaceted experiments and photothermal simulations based analysis of laser induced graphene and its fibers

The interaction of CO2 laser with polyimide results in the formation of laser-induced graphene (LIG) and other morphological transitions based on laser parameters, such as Laser-induced fibers (LIF) on the surface. However, a fundamental investigation of LIF, its properties and potential have not been explored until now. We aim therefore to provide novel insights into the LIF by characterization of its structural, electrical, electrochemical, and mechanical properties. Four different morphologies were identified depending on the laser parameters and the temperature required for their formation were quantified by FEM model. Minimum temperatures of 1800 K were required to form LIG and around 2600 to 5000 K to form LIF. High heterogeneity of the LIF along thickness due to temperature gradients, and the existence of sheet structures underneath the fibers were identified. Due to the loosely bound nature of fibers, LIF dispersion was prepared by ultrasonication to functionalize the carbon electrode for electrochemical characterization. The modification with LIF on the electrodes enhanced the electrochemical response of the electrode towards standard redox couple which confirmed the conductive nature of the fibers. This work provides a solid basis for the versatile tuning of the behavior and properties of LIF for potential applications.

Influencing the morphological stability of MOVPE-grown β-Ga2O3 films by O2/Ga ratio

The morphology evolution of (100) β-Ga2O3 films grown by metalorganic vapor phase epitaxy (MOVPE) is studied by atomic force microscopy (AFM). In particular, when grown under a high O2/Ga ratio (O2/Ga = 1250) and above a thickness of 350 nm, these films exhibit striking morphological instabilities, including step meandering and bunching, which contribute significantly to surface roughening. Transmission electronic microscopy (TEM) measurements reveal a morphological transition on the growing surface with a coexistence of step-flow and step-bunching growth modes resulting from these instabilities. In contrast, growth conditions with low O2/Ga ratios (O2/Ga = 350) effectively suppress meandering and bunching instabilities, resulting in films with excellent electrical properties. These observations are rationalized through the Burton-Cabrera-Frank (BCF) theory and Bales-Zangwill (BZ) instability (Gibbs-Thompson effect and Mullins-Sekerka instability) , thus bridging theoretical models and the experimental results.

Performance evaluation of biodegradable polymer PHBV and PBAT blends with adjustable melt flow behaviour, heat deflection temperature, and morphological transition

AbstractMelt blending is a reliable and well‐demonstrated strategy for improving the mechanical, thermal, rheological, and surface properties of biopolymers. Poly(hydroxy‐3‐butyrate‐co‐3‐hydroxyvalerate) (PHBV) and poly(butylene adipate‐co‐terephthalate) (PBAT) are the two popular choices for blending polymers due to their diverse properties and complementary soil biodegradable behaviour. Due to their immiscibility, however, blending with the help of processing additives is necessary to reap the most significant benefits from this process and to avoid immiscibility issues. This study utilized the additives (peroxides and epoxy‐based chain extender) to compatibilize the biodegradable polymers PHBV and PBAT in a 60:40 blending ratio. The tensile strength and Young's modulus of the PHBV/PBAT(60/40) blend were improved by 32% and 64%, respectively, after adding a combination of peroxide (0.02 phr) and chain extender (0.3 phr) due to the formation of a complex network structure with increased chain length. The positive effect of an additive addition was also reflected by a 30°C increment in heat deflection temperature of biodegradable blend due to its high modulus value as supported by mechanical properties. The combined action of a peroxide and chain extender demonstrated a significantly higher complex viscosity of the PHBV/PBAT(60/40) blend due to the formation of a crosslinked polymer network as analyzed by rheological analysis. Our research demonstrated the effect of additives and their combined impact on analytical properties of PHBV/PBAT(60/40) blend to guide future work in improving their candidature to serve as a drop‐in solution in replacing non‐biodegradable petro‐based plastic products.

Polyelectrolyte-protein synergism: pH-responsive polyelectrolyte/insulin complexes as versatile carriers for targeted protein and drug delivery

The co-assembly of polyelectrolytes (PE) with proteins offers a promising approach for designing complex structures with customizable morphologies, charge distribution, and stability for targeted cargo delivery. However, the complexity of protein structure limits our ability to predict the properties of the formed nanoparticles, and our goal is to identify the key triggers of the morphological transition in protein/PE complexes and evaluate their ability to encapsulate multivalent ionic drugs. A positively charged PE can assemble with a protein at pH above isoelectric point due to the electrostatic attraction and disassemble at pH below isoelectric point due to the repulsion. The additional hydrophilic block of the polymer should stabilize the particles in solution and enable them to encapsulate a negatively charged drug in the presence of PE excess. We demonstrated that diblock copolymers, poly(ethylene oxide)-block-poly(N,N-dimethylaminoethyl methacrylate) and poly(ethylene oxide)-block-poly(N,N,N-trimethylammonioethyl methacrylate), consisting of a polycation block and a neutral hydrophilic block, reversibly co-assemble with insulin in pH range between 5 and 8. Using small-angle neutron and X-ray scattering (SANS, SAXS), we showed that insulin arrangement within formed particles is controlled by intermolecular electrostatic forces between protein molecules, and can be tuned by varying ionic strength. For the first time, we observed by fluorescence that formed protein/PE complexes with excess of positive charges exhibited potential for encapsulating and controlled release of negatively charged bivalent drugs, protoporphyrin-IX and zinc(II) protoporphyrin-IX, enabling the development of nanocarriers for combination therapies with adjustable charge, stability, internal structure, and size.

Drug-induced transitions from micelles to vesicles in ionic surfactant solutions

Surfactant solutions play key roles in scientific research and technological applications. Here we investigated solutions that combined an ionic surfactant, Cetylpyridinium Chloride (CPyCl), with a non-steroidal, anti-inflammatory drug, Sodium Diclofenac (Diclo). The study covered a wide range of compositions and utilized both rheology and cryogenic-Electron Microscopy (cryo-EM). The solutions were prepared at three different concentrations of CPyCl: 5.0 mM, 16.7 mM and 33.0 mM, and we maintained the ratio of surfactant to salt, R=CPyCl/Diclo, within the range of 0.24<R<1.2. Linear viscoelasticity was measured at 25°C. The use of dilute solutions allowed for detailed cryo-EM imaging. By tracking the evolution of the zero-frequency viscosity as a function of Diclo concentration, we identified distinct regions of different rheological responses. The correlation between frequency sweep data and cryo-EM images enabled us to link these regions to specific morphological transitions ranging from spherical micelles to long and entangled wormlike micelles, to branched networks and, eventually, to perforated vesicles. For some systems, we were able to measure the complete spectrum of relaxation times, including the shortest characteristic Rouse time at high frequencies, previously only achieved by Diffusive Wave Spectroscopy. The use of existing models to evaluate the relevant important microstructural parameters such as entanglement, contour, and persistence lengths allowed us to establish a clear correlation between the microstructural parameters derived through rheology and the insights from the cryo-EM analysis.