Conformation Of Macromolecules Research Articles

TRIP13: A promising cancer immunotherapy target.

The tumor microenvironment (TME) facilitates tumor development through intricate intercellular signaling, thereby supporting tumor growth and suppressing the immune response. Thyroid hormone receptor interactor 13 (TRIP13), an AAA+ ATPase, modulates the conformation of client macromolecules, consequently influencing cellular signaling pathways. TRIP13 has been implicated in processes such as proliferation, invasion, migration, and metastasis during tumor progression. Recent studies have revealed that TRIP13 also plays a role in immune response suppression within the TME. Thus, inhibiting these functions of TRIP13 could potentially enhance immune responses and improve the efficacy of immune checkpoint inhibition. This review summarizes the recent research progress of TRIP13 and discusses the potential of targeting TRIP13 to improve immune-based therapies for patients with cancer.

Advantages of Pyrene Excimer Formation (PEF) over Fluorescence Resonance Energy Transfer (FRET) for Probing the Conformation of Macromolecules in Solution

Advantages of Pyrene Excimer Formation (PEF) over Fluorescence Resonance Energy Transfer (FRET) for Probing the Conformation of Macromolecules in Solution

STMP and PVPA as Templating Analogs of Noncollagenous Proteins Induce Intrafibrillar Mineralization of Type I Collagen via PCCP Process.

The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogs of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogs such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, STMP-Ca and PVPA-Ca complexes are proposed to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and in vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic 3D stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization.

Effect of production technologies on the properties and structure of PTFE-based composites

In the development of polymer composite materials, it is crucial to use various technological methods for introducing fillers into the structure of the base polymer, by different activation technologies of energy exposure. In this study, the processes of structure formation of polymer composite materials based on polytetrafluoroethylene and discrete hydrate cellulose carbon fibers, depending on the production technology, were investigated by scanning electron microscopy. We considered joint mechanical activation of components and passing the powder mixture through laboratory rollers. To understand the processes occurring in the friction process of the developed PCM, surface studies before and after friction by infrared spectroscopy were carried out. We found that during the friction process, depending on the friction mode, the spiral conformation of the PTFE macromolecules changes. An increase in the sliding velocity and the load during PCM friction leads to a change in the spiral conformation of macromolecules with a transition from 136 to a more stable conformation 157. We also found that the combination of technologies for joint mechanical activation of components and rolling of a powder mixture are technological techniques that can increase the structural activity of discrete hydrocarbons and intensify the adhesive interaction at the polymer-filler phase interface, which leads to an increase in the resistance of composites to creep and wear. The developed technological approaches can be used in the production of fluorocomposites containing not only carbon but also other types of fibers.

A Study on How Conformation Entropy of Attached Macromolecules Drives Polymeric Collapse and Protein Folding

AbstractThe conformation of macromolecules attached to a surface is influenced by both their excluded volume and steric forces. Here, self‐avoiding random walk simulations are used to evaluate the occurrence of various conformations as a function of the number of monomeric units to estimate the effect of conformational entropy of a tethered chain. Then, a more realistic scenario is assessed, which can more accurately reproduce the shape of a tethered macromolecule. The simulations presented here confirm that it is more likely for a polymer to undergo a collapse conformation rather than a stretched one, as a collapse conformation can be realized in more different ways. Also, they confirm the “mushroom” shape of polymers close to a surface. From this simple approach, the conformation entropy of a model 100‐unit polymer close to a surface is estimated to contribute with over 129 toward its collapse. This conformation entropy is higher than that of typical hydrogen bonds and even barriers that keep proteins folded. As such, entropic collapse of macromolecules plays an important role in realizing the mushroom shape of attached polymers and can be the driving force in protein folding, while the polypeptide chain emerges from the ribosome.

Accurate Determination of the Average Rate Constant of Pyrene Excimer Formation for Pyrene-Labeled Macromolecules from the Analysis of Individual Fluorescence Decays with Sums of Exponentials.

The average rate constant (⟨k⟩) for pyrene excimer formation (PEF) between an excited and a ground-state pyrenyl label covalently attached to a pyrene-labeled macromolecule (PyLM) has been found to be an ideal parameter to probe macromolecular conformations due to its proportionality to the local concentration ([Py]loc) of pyrenyl labels in PyLM. To date, ⟨k⟩ has only been determined with the model-free analysis (MFA) involving the global analysis of the pyrene monomer and excimer fluorescence decays of PyLM. Unfortunately, the MFA is computationally demanding which prevents its widespread use. To circumvent this complication, a methodology is introduced that involves the analysis of individual fluorescence decays with sums of exponentials (SoE), which are commonly used in the analysis packages of commercial time-resolved fluorometers. The individual fluorescence decays of the pyrene monomer acquired with 286 PyLM were analyzed with a SoE to yield ⟨kSoE-M⟩. The strong correlation between ⟨kSoE-M⟩ and ⟨kMF⟩ obtained from the global MFA indicated that ⟨kSoE-M⟩ was a good representation of ⟨k⟩. Furthermore, the AE-/AE+ ratio, equal to the ratio of the sum of the negative pre-exponential factors over the sum of the positive pre-exponential factors, was determined by fitting the individual pyrene excimer fluorescence decays of the 286 PyLM with a SoE. AE-/AE+ was found to take a value between -1.0 and -0.8, indicating that the pyrenyl labels were not aggregated. This result indicated that [Py]loc was well described by ⟨kSoE-M⟩, so that ⟨kSoE-M⟩ could be used to describe the conformation of macromolecules in the same manner as ⟨kMF⟩. Consequently, the methodology based on the analysis of individual fluorescence decays with sums of exponentials to determine ⟨kSoE-M⟩ and AE-/AE+ provides a robust alternative to the use of the MFA for the study of PyLM to many scientists interested in the characterization of macromolecular conformations.

Influence of nature and macromolecular characteristics of carrier polymer on immobilization of bolaform ions

The study of the interactions of polyelectrolytes with organic ions and especially with ions of physiologically active substances is of particular. There are wide ranges of polymers used for these purposes, the most convenient “substrate” is considered to be synthetic carriers that are easily regulated during production. The object of research was the antiprotozoal drug azidine, widely used in veterinary practice, which, when dissolved in water, forms a complex bolaform cation: 4.41-diamidinodiazoaminobenzene. To develop a prolonged dosage form for veterinary medicine, the binding of this substance with various synthetic polymers such as polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic, and polymethacrylic acids are important. In addition; their copolymers, was studied using physical and chemical methods. The influence of the nature of the carrier polymer, the molecular weight, and the conformation of macromolecules on the process of binding organic ions were also examined.The results obtained were confirmed by in vivo tests on cattle. A pattern is shown between the strength of the bond of the drug substance with the polymer carrier and the time of its preventive action.

WATER PURIFICATION FROM HEAVY METAL IONS USING LIME AND PHMG

The method of metal ions' chemical precipitation using polyhexamethylene guanidine (PHMG) and calcium oxide (CaO) was employed for extracting metal ions from concentrated solutions. The order of reagent introduction was found to be crucial in the extraction process, with the best extraction efficiency observed when PHMG was added to water before CaO. This order of addition facilitated the polyelectrolyte effect, resulting in the unfolded conformation of macromolecules and enhancing their interaction with metal ions in solution. Optimal dosage ranges were determined, coinciding with the concentration interval of the polyelectrolyte effect, which maximized the flocculation ability and complex formation of PHMG. The combined use of PHMG and CaO, along with variations in pH, achieved high degrees of metal ion removal (>99%) in a single stage of solution treatment, except for chromium (Cr3+) and cobalt (Co2+). The surface activity of PHMG and ability to transfer metal ions as metal-polymer complexes supported its use in the flotation method for extracting heavy metal ions from low-concentration aqueous solutions. The kinetics of PHMG and metal ion removal by flotation showed rapid binding of metal ions to polymer macromolecules, and regression equations were established to describe the kinetics. The residual concentrations of metal ions after flotation met regulatory sanitary and environmental requirements for wastewater and drinking water. A two-stage scheme for heavy metal ion extraction was developed, involving chemical precipitation and flotation extraction, with a pilot plant designed and manufactured for testing. During wastewater treatment in an electroplating production setting, metal ion concentrations that complied with regulatory standards were achieved.

Rearrangement of the Conformations of Polyampholitic Macromolecules on the Surface of a Charged Spherical Metal Nanoparticle in an Alternating Electric Field: Molecular Dynamic Simulation

Rearrangement of the Conformations of Polyampholitic Macromolecules on the Surface of a Charged Spherical Metal Nanoparticle in an Alternating Electric Field: Molecular Dynamic Simulation

Rearrangement of the Conformations of Polyampholitic Macromolecules on the Surface of a Charged Spherical Metal Nanoparticle in an Alternating Electric Field: Molecular Dynamic Simulation

The rearrangement of the conformational structure of polyampholytic polypeptides on the surface of a charged spherical gold nanoparticle with its polarity intermittently changing over time was studied using molecular dynamics modeling. The angular distributions of the polypeptide atoms, as well as the radial distributions of the macrochain atomic density in the equatorial region of the nanoparticle with differentiation according to the types of links, were calculated. The polyampholyte shell acquired an annular shape, and the resulting macromolecular ring was located around the charged nanoparticle perpendicularly to the vector of the external electric field strength. With an increase in the charge of the nanoparticle, the ring belt was ordered according to the types of macrochain links, forming concentric annular layers. The diameter of the macromolecular ring depended on the law of distribution of charged units in the macrochain. At elevated temperatures the annular macromolecular ring was deformed at the moments of the highest polarization of the nanoparticle.

A method for restoring signals and revealing individual macromolecule states in cryo-ET, REST

Cryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer the knowledge to restore signals in cryo-ET. Test results on the simulated and real cryo-ET datasets show that REST performs well in denoising and compensating the missing wedge information. The application in dynamic nucleosomes, presenting either in the form of individual particles or in the context of cryo-FIB nuclei section, indicates that REST has the capability to reveal different conformations of target macromolecules without subtomogram averaging. Moreover, REST noticeably improves the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.

Properties of Nanocomposites Based on Platinum Nanoparticles Stabilized by Chitosan

AbstractPlatinum nanoparticles were obtained chemically in acetic acid solutions of chitosan from the precursor H2PtCl6 using sodium borohydride as a reducing agent with simultaneous UV irradiation. The compositions were studied by SAXS, TEM, dynamic light scattering, FTIR‐spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, and atomic force microscopy. Nanoparticles are characterized by a narrowly dispersed size distribution while the effect of the conformation of chitosan macromolecules on their characteristics is manifested. The SAXS method showed that in a chitosan solution with a semi‐flexible coil conformation of macromolecules, 96.8 % of the formed nanoparticles are characterized by an average radius of 1.4 nm. According to the TEM results, platinum nanoparticles are characterized by a crystal structure and a particle diameter of about 1.3–5.0 nm. A different picture is observed for platinum nanoparticles formed in chitosan with the rigid rod conformation of macromolecules – only 91 % of platinum nanoparticles had an average radius of 1.4 nm. The TEM method showed these nanoparticles turned out to be about 1 nm in size, and they did not crystallize, but remained amorphous. The introduction of platinum nanoparticles into the polysaccharide matrix significantly shifts the glass transition temperature of chitosan toward lower values by 20 and 10 °C respectively, and increases the tensile strength of the composites by 35 MPa.

Effects of Terahertz Radiation on the Aggregation of Alzheimer’s Aβ42 Peptide

The pathophysiology of Alzheimer's disease is thought to be directly linked to the abnormal aggregation of β-amyloid (Aβ) in the nervous system as a common neurodegenerative disease. Consequently, researchers in many areas are actively looking for factors that affect Aβ aggregation. Numerous investigations have demonstrated that, in addition to chemical induction of Aβ aggregation, electromagnetic radiation may also affect Aβ aggregation. Terahertz waves are an emerging form of non-ionizing radiation that has the potential to affect the secondary bonding networks of biological systems, which in turn could affect the course of biochemical reactions by altering the conformation of biological macromolecules. As the primary radiation target in this investigation, the in vitro modeled Aβ42 aggregation system was examined using fluorescence spectrophotometry, supplemented by cellular simulations and transmission electron microscopy, to see how it responded to 3.1 THz radiation in various aggregation phases. The results demonstrated that in the nucleation aggregation stage, 3.1 THz electromagnetic waves promote Aβ42 monomer aggregation and that this promoting effect gradually diminishes with the exacerbation of the degree of aggregation. However, by the stage of oligomer aggregation into the original fiber, 3.1 THz electromagnetic waves exhibited an inhibitory effect. This leads us to the conclusion that terahertz radiation has an impact on the stability of the Aβ42 secondary structure, which in turn affects how Aβ42 molecules are recognized during the aggregation process and causes a seemingly aberrant biochemical response. Molecular dynamics simulation was employed to support the theory based on the aforementioned experimental observations and inferences.

Simulation of the processes of plasma modification and vacuum metallization of polymer materials by the method of molecular dynamics

The article presents the results of the development of molecular dynamics models of modifications of polypropylene (PP) material in the plasma of a radio-frequency (RF) discharge and a copper coating deposit by magnetron sputtering on the surface of a polyethylene (PE) material. The model of the RF plasma modification process describes changes in the surface layers of the PP material upon interaction with low-energy plasma ions: the nature of the breaking of covalent bonds in macromolecules, the chemical composition of sputtered particles, and changes in the ordering of the supramolecular structure. The model of the vacuum metallization process describes the processes of the introduction of metal atoms into the polymer structure, the change in the conformation of macromolecules, the formation of macroradicals with uncompensated chemical bonds, and the formation of an interfacial layer between the polymer and the metal coating.

Высокопрочные фторопластовые композиты с повышенной сопротивляемостью к деформациям под нагрузкой

This paper presents the results of research on the development of technology for plastic deformation of polymer blanks based on polytetrafluoroethylene (PTFE) and carbon fibers of the UVIS-AK-P brand in order to increase their strength and creep resistance. The dependence of the physico-mechanical and tribotechnical characteristics of the obtained composites is investigated and compared with a composite of the same composition, but obtained using a previously developed technology. It is established that the use of plastic deformation technology for the properties of PCM based on PTFE and carbon fibers of the brand UVIS-AK-P is an effective solution for obtaining high-strength, wear-resistant composites, characterized by increased resistance to tensile loads. The developed composites obtained using plastic deformation are characterized by 3 times increased tensile strength and 22 – 29 times reduced creep compared to the original PTFE obtained by standard technology. Structural studies of the technology of plastic deformation of polymer blanks have shown that this technology leads to the orientation of the carbon fiber (CF) in the direction of the flow of the material and a change in the spiral conformation of macromolecules with a transition to a more stable conformation, which favorably affects its operational properties. The use of this method will make it possible to obtain high-strength polymer materials with increased resistance to deformation, promising for use for loading schemes with high tensile loads.

Probing the inner local density of complex macromolecules by pyrene excimer formation.

The direct relationship existing between the average rate constant 〈k〉 for pyrene excimer formation and the local concentration [Py]loc of ground-state pyrenyl labels covalently attached to a macromolecule was established for 55 pyrene-labeled macromolecules (PyLM). These PyLM belonged to three different families of macromolecules with the first representing short monodisperse linear chains end-labeled with pyrene (polystyrene, poly(ethylene oxide), and poly(N-isopropyl acrylamide)), the second representing long polydisperse linear chains randomly labeled with pyrene (poly(methyl acrylate), poly(methyl methacrylate), polystyrene, poly(butyl methacrylate), poly(methoxyethyl methacrylate), and poly(N-isopropyl acrylamide)), and the third being comprised of two series of pyrene end-labeled low generation dendrimers with a bis(hydroxymethyl)propionic acid or a polyamidoamine backbone. The assumption, that the polymeric segments probed by an excited pyrenyl label covalently attached to one of these macromolecules obeyed Gaussian statistics, enabled the calculation of their square root average squared end-to-end distance (LPy), which was applied to calculate [Py]loc. The log-log plots of 〈k〉 as a function of [Py]loc yielded straight lines with a slope of unity for all families of macromolecules studied in four different organic solvents demonstrating the validity and generality of the 〈k〉-vs.-[Py]loc relationship. Since an experimentalist knows how the the pyrenyl labels are covalently attached onto a macromolecule, [Py]loc offers a means to probe the local density of a macromolecule, which can be employed to characterize its conformation in solution. Consequently, the 〈k〉-vs.-[Py]loc relationship provides a novel experimental means to probe the conformation of macromolecules which should establish pyrene excimer formation as an appealing method for conformational studies of macromolecules in solution, which should nicely complement scattering techniques.

Temperature Effect on Ionic Polymers Removal from Aqueous Solutions Using Activated Carbons Obtained from Biomass

The main aim of this study was the determination of temperature influence on adsorption mechanisms of anionic poly(acrylic acid) (PAA) and cationic polyethylenimine (PEI) on the surface of activated carbons (AC) obtained via chemical activation of nettle (NE) and sage (SA) herbs. All measurements were performed at pH 3 at three temperature values, i.e., 15, 25 and 35 °C. The adsorption/desorption of these polymers from single and mixed solution of adsorbates was also investigated. The viscosity studies were additionally performed to obtain hydrodynamic radius values characterizing polymeric macromolecules conformation in the solution. These data are very important for the explanation of changes of linear dimensions of polymer chains with the rise of temperature caused by the modification of polymer-solvent interactions. Moreover, the XPS studies for the systems showing the highest adsorbed amounts in the specific temperature conditions were carried out. These were the systems containing PEI, PAA and NE-AC activated carbon at 25 °C. In such a case, the maximum adsorption capacity towards PAA macromolecules from a single solution of adsorbate reaches the value of 198.12 mg/g. Additionally, the thermodynamic parameters including the free energies of adsorption, as well as changes in free enthalpy and entropy were calculated.

Micro-structure and tensile properties of microfluidic spinning konjac glucomannan and sodium alginate composite bio-fibers regulated by shear and elongational flow: experiment and multi-scale simulation

Microfluidic spinning has been widely used to produce bio-fibers with excellent tensile performances by regulating the conformation of biological macromolecules. However, the effect of channel shapes on fiber tensile performances is unclear. In this study, bio-fibers were prepared using konjac glucomannan and sodium alginate by five channels. The micro-morphology and tensile performance of fibers were characterized and measured. Then, the dynamical behaviours of macromolecule clusters in flow fields were simulated by multi-scale numerical methods. The results show that the elongational flow with increasing extension rates produced fibers with a tensile strength of 32.34 MPa and a tensile strain of 18.72 %, which were 1.37 and 1.55 times that for a shear flow, respectively. The difference in tensile performances was attributed to the micro-morphology regulated by flow fields. The continuously increasing extension rate of flow was more effective than the shear rate or the maximum extension rate for the stretching of macromolecule clusters. We conclude that the channel shapes significantly influence flow fields, dynamical behaviours of molecule clusters, the morphology of fibers, and tensile performances. This study provides a novel numerical method and understanding of microfluidic spinning, which will promote the optimization and applications of bio-fibers.

Measuring Structural Changes in Cytochrome c under Crowded Conditions Using In Vitro and In Silico Approaches.

It is known from in vitro studies that macromolecular crowding in the cell effects protein structure, stability and function; but predictive studies are relatively unexplored. There are few reports where the effect of various crowder mixtures has been exploited to discern their combined effect on the structural stability of proteins. These studies are more significant because their effect can mimicked with in vivo conditions, where the environment is heterogeneous. Effects of two crowders, polyethylene glycol (PEG 400 Da), and its monomer ethylene glycol (EG) alone and in mixture on the structural stability of cytochrome c (cyt c) were determined using various spectroscopic and bioinformatics tools. The main conclusions of our study are (i) the monomer EG has a kosmotropic effect on the protein (stabilizes the protein), and has no significant effect on the tertiary structure; (ii) PEG 400 destabilizes the structure as well as the stability of the protein; and (iii) EG counteracts the destabilizing effect of PEG 400. From this investigation, it seems evident that proteins may fold or unfold in the crowded environment of the cell where various interactions assist them to maintain their structure for their functions. Bioinformatics approaches were also used to support all of the in vitro observations. Cyt c is functional protein; if the structure of the protein is modulated due to change in the environment its nature of function will also change. Our research addresses the question by modulating the environment around the protein, and the macromolecule (protein) conformation dynamics and interaction study via in vitro and in silico approaches which indirectly compares with that of the environment in-cellular milieu, which is highly crowded.

Advances in the exact nuclear Overhauser effect 2018-2022.

The introduction of the exact nuclear Overhauser enhancement (eNOE) methodology to solution-state nuclear magnetic resonance (NMR) spectroscopy results in tighter distance restraints from NOEs than in convention analysis. These improved restraints allow for higher resolution in structure calculation and even the disentanglement of different conformations of macromolecules. While initial work primarily focused on technical development of the eNOE, structural studies aimed at the elucidation of spatial sampling in proteins and nucleic acids were published in parallel prior to 2018. The period of 2018-2022 saw a continued series of technical innovation, but also major applications addressing biological questions. Here, we review both aspects, covering topics from the implementation of non-uniform sampling of NOESY buildups, novel pulse sequences, adaption of the eNOE to solid-state NMR, advances in eNOE data analysis, and innovations in structural ensemble calculation, to applications to protein, RNA, and DNA structure elucidation.