Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 11.266
1.
Phys Rev Lett ; 132(20): 208401, 2024 May 17.
Article En | MEDLINE | ID: mdl-38829088

In many biopolymer solutions, attractive interactions that stabilize finite-sized clusters at low concentrations also promote phase separation at high concentrations. Here we study a model biopolymer system that exhibits the opposite behavior, whereby self-assembly of DNA oligonucleotides into finite-sized, stoichiometric clusters tends to inhibit phase separation. We first use microfluidics-based experiments to map a novel phase transition in which the oligonucleotides condense as the temperature increases at high concentrations of divalent cations. We then show that a theoretical model of competition between self-assembly and phase separation quantitatively predicts changes in experimental phase diagrams arising from DNA sequence perturbations. Our results point to a general mechanism by which self-assembly shapes phase boundaries in complex biopolymer solutions.


DNA , Models, Chemical , Phase Transition , DNA/chemistry , Hot Temperature , Oligonucleotides/chemistry , Phase Separation
2.
J Chem Phys ; 160(21)2024 Jun 07.
Article En | MEDLINE | ID: mdl-38847600

Liquid-liquid phase separation in biology has recently been shown to play a major role in the spatial control of biomolecular components within the cell. However, as they are phase transitions, these processes also display nontrivial dynamics. A model phase-separating system of DNA nanostars provides unique access to nucleation physics in a biomolecular context, as phase separation is driven near room temperature by highly thermo-responsive DNA hybridization and at modest DNA concentrations. By measuring the delay time for phase-separated droplets to appear, we demonstrate that the dynamics of DNA nanostar phase separation reflect that of a metastable binary mixture of patchy particles. For sufficiently deep temperature quenches, droplets undergo spinodal decomposition and grow spontaneously, driven by Brownian motion and coalescence of phase-separated droplets, as confirmed by comparing experimental measurements to particle-based simulations. Near the coexistence boundary, droplet growth slows substantially, indicative of a nucleation process. The temperature dependence of droplet appearance times can be predicted by a classical nucleation picture with mean field exponents and demonstrates that a theory previously used to predict equilibrium phase diagrams can also distinguish spinodal and nucleation dynamical regimes. These dynamical principles are relevant to behaviors associated with liquid-liquid phase separating systems, such as their spatial patterning, reaction coupling, and biological function.


DNA , Phase Transition , DNA/chemistry , Temperature , Models, Chemical , Nucleic Acid Hybridization , Nanostructures/chemistry
3.
J R Soc Interface ; 21(214): 20240022, 2024 May.
Article En | MEDLINE | ID: mdl-38715321

Using a three-dimensional model of cell monolayers, we study the spatial organization of active stress chains as the monolayer transitions from a solid to a liquid state. The critical exponents that characterize this transition map the isotropic stress percolation onto the two-dimensional random percolation universality class, suggesting short-range stress correlations near this transition. This mapping is achieved via two distinct, independent pathways: (i) cell-cell adhesion and (ii) active traction forces. We unify our findings by linking the nature of this transition to high-stress fluctuations, distinctly linked to each pathway. The results elevate the importance of the transmission of mechanical information in dense active matter and provide a new context for understanding the non-equilibrium statistical physics of phase transition in active systems.


Cell Adhesion , Models, Biological , Cell Adhesion/physiology , Stress, Mechanical , Phase Transition
4.
Sci Adv ; 10(19): eadi8433, 2024 May 10.
Article En | MEDLINE | ID: mdl-38718115

Cell deformability is an essential determinant for tissue-scale mechanical nature, such as fluidity and rigidity, and is thus crucial for tissue homeostasis and stable developmental processes. However, large-scale simulations of deformable cells have been restricted to those of polygonal-shaped cells, limiting our understanding of populations of arbitrarily deformable cells, such as mesenchymal, amoeboid cells, and nonconfluent epithelial cells. Here, we present an efficient approach for simulating large populations of nonpolygonally deformable cells with considerably higher computational efficiency than existing methods. Using the method, we demonstrate that the densely packed active cell population interacting via excluded volume interactions exhibits a fluid-to-fluid transition. An experimentally measurable index of topological defects, defined using the number of neighboring cells, is also proposed to characterize this transition. This study provides a flexible approach to tissue-scale cell population and a broader perspective on the biological fluid phases.


Models, Biological , Phase Transition , Humans , Cell Shape , Computer Simulation , Epithelial Cells/metabolism , Epithelial Cells/cytology
5.
Cryo Letters ; 45(4): 231-239, 2024.
Article En | MEDLINE | ID: mdl-38809787

BACKGROUND: Transformation of state diagrams of cryoprotectant solutions under the influence of weak intramolecular interactions was considered. MATERIALS AND METHODS: Phase states of aqueous glycerol and DMSO solutions within temperature range +25 to -150 degree С were studied using method of volumetric scanning tensodilatometry. Temperatures below which hydrogen bonds significantly affect crystallization-melting kinetics of such solutions were determined. RESULTS: Principles for plotting of state diagram for binary solutions with weak intermolecular interaction of the components were set up. The study demonstrates that in such solutions formation of clusters based on ice microcrystals and cryoprotectant occurs. Based on the obtained results, state diagrams for glycerol and DMSO aqueous solutions were plotted. These diagrams include area of cluster phase existence and differ fundamentally from those describing eutectic crystallization. CONCLUSION: Nanostructures occurring in cryoprotectant solutions during their cooling were analyzed. Difference between these structures and classical solid phase eutectics were demonstrated. Doi.org/10.54680/fr24410110712.


Cryoprotective Agents , Crystallization , Dimethyl Sulfoxide , Glycerol , Hydrogen Bonding , Cryoprotective Agents/chemistry , Glycerol/chemistry , Dimethyl Sulfoxide/chemistry , Solutions , Water/chemistry , Phase Transition
6.
Prog Mol Biol Transl Sci ; 206: 143-182, 2024.
Article En | MEDLINE | ID: mdl-38811080

Liquid-liquid phase separation (LLPS) refers to the phenomenon, where a homogeneous solution spontaneously undergoes a transition into two or more immiscible phases. Through transient weak multivalent macromolecular interactions, a homogeneous solution can spontaneously separate into two phases: one rich in biomolecules and the other poor in biomolecules. Phase separation is believed to serve as the physicochemical foundation for the formation of membrane-less organelles (MLOs) and bio-molecular condensates within cells. Moreover, numerous biological processes depend on LLPS, such as transcription, immunological response, chromatin architecture, DNA damage response, stress granule formation, viral infection, etc. Abnormalities in phase separation can lead to diseases, such as cancer, neurodegeneration, and metabolic disorders. LLPS is regulated by various factors, such as concentration of molecules undergoing LLPS, salt concentration, pH, temperature, post-translational modifications, and molecular chaperones. Recent research on LLPS of biomolecules has progressed rapidly and led to the development of databases containing information pertaining to various aspects of the biomolecule separation analysis. However, more comprehensive research is still required to fully comprehend the specific molecular mechanisms and biological effects of LLPS.


Phase Transition , Humans , Animals , Liquid-Liquid Extraction , Amyloid/chemistry , Amyloid/metabolism , Phase Separation
7.
Acta Biomater ; 181: 469-482, 2024 Jun.
Article En | MEDLINE | ID: mdl-38723926

Medium-entropy alloys (MEAs) typically exhibit outstanding mechanical properties, but their high Young's modulus results in restricted clinical applications. Mismatched Young's modulus between implant materials and human bones can lead to "stress shielding" effects, leading to implant failure. In contrast, ß-Ti alloys demonstrate a lower Young's modulus compared to MEAs, albeit with lower strength. In the present study, based on the bimodal grain size distribution (BGSD) strategy, a series of high-performance TiZrNbTa/Ti composites are obtained by combining TiZrNbTa MEA powders with nano-scale grain sizes and commercially pure Ti (CP-Ti) powders with micro-scale grain sizes. Concurrently, Zr, Nb, and Ta that are ß-Ti stabilizer elements diffuse into Ti, inducing an isomorphous transformation in Ti from the high Young's modulus α-Ti phase to the low Young's modulus ß-Ti phase at room temperature, optimizing the mechanical biocompatibility. The TiZrNbTa/ß-Ti composite demonstrates a yield strength of 1490 ± 83 MPa, ductility of 20.7 % ± 2.9 %, and Young's modulus of 87.6 ± 1.6 GPa. Notably, the yield strength of the TiZrNbTa/ß-Ti composite surpasses that of sintered CP-Ti by 2.6-fold, and its ductility outperforms TiZrNbTa MEA by 2.3-fold. The Young's modulus of the TiZrNbTa/ß-Ti composite is reduced by 28 % and 36 % compared to sintered CP-Ti and TiZrNbTa MEA, respectively. Additionally, it demonstrates superior biocompatibility compared to CP-Ti plate, sintered CP-Ti, and TiZrNbTa MEA. With a good combination of mechanical properties and biocompatibility, the TiZrNbTa/ß-Ti composite exhibits significant potential for clinical applications as metallic biomaterials. STATEMENT OF SIGNIFICANCE: This work combines TiZrNbTa MEA with nano-grains and commercially pure Ti with micro-grains to fabricate a TiZrNbTa/ß-Ti composite with bimodal grain-size, which achieves a yield strength of 1490 ± 83 MPa and a ductility of 20.7 % ± 2.9 %. Adhering to the ISO 10993-5 standard, the TiZrNbTa/ß-Ti composite qualifies as a non-cytotoxic material, achieving a Class 0 cytotoxicity rating and demonstrating outstanding biocompatibility akin to commercially pure Ti. Drawing on element diffusion, Zr, Nb, and Ta serve not only as solvent atoms to achieve solid-solution strengthening but also as stabilizers for the transformation of the ß-Ti crystal structure. This work offers a novel avenue for designing advanced biomedical Ti alloys with elevated strength and plasticity alongside a reduced Young's modulus.


Alloys , Biocompatible Materials , Materials Testing , Titanium , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Elastic Modulus , Humans , Niobium/chemistry , Niobium/pharmacology , Zirconium/chemistry , Zirconium/pharmacology , Phase Transition , Mice
8.
Soft Matter ; 20(19): 4007-4014, 2024 May 15.
Article En | MEDLINE | ID: mdl-38690757

Biology exploits biomacromolecular phase separation to form condensates, known as membraneless organelles. Despite significant advancements in deciphering sequence determinants for phase separation, modulating these features in vivo remains challenging. A promising approach inspired by biology is to use post-translational modifications (PTMs)-to modulate the amino acid physicochemistry instead of altering protein sequences-to control the formation and characteristics of condensates. However, despite the identification of more than 300 types of PTMs, the detailed understanding of how they influence the formation and material properties of protein condensates remains incomplete. In this study, we investigated how modification with myristoyl lipid alters the formation and characteristics of the resilin-like polypeptide (RLP) condensates, a prototypical disordered protein with upper critical solution temperature (UCST) phase behaviour. Using turbidimetry, dynamic light scattering, confocal and electron microscopy, we demonstrated that lipidation-in synergy with the sequence of the lipidation site-significantly influences RLPs' thermodynamic propensity for phase separation and their condensate properties. Molecular simulations suggested these effects result from an expanded hydrophobic region created by the interaction between the lipid and lipidation site rather than changes in peptide rigidity. These findings emphasize the role of "sequence context" in modifying the properties of PTMs, suggesting that variations in lipidation sequences could be strategically used to fine-tune the effect of these motifs. Our study advances understanding of lipidation's impact on UCST phase behaviour, relevant to proteins critical in biological processes and diseases, and opens avenues for designing lipidated resilins for biomedical applications like heat-mediated drug elution.


Peptides , Peptides/chemistry , Hydrophobic and Hydrophilic Interactions , Insect Proteins/chemistry , Insect Proteins/metabolism , Phase Transition , Amino Acid Sequence , Protein Processing, Post-Translational
9.
Nat Commun ; 15(1): 4408, 2024 May 23.
Article En | MEDLINE | ID: mdl-38782886

Phase separation and percolation contribute to phase transitions of multivalent macromolecules. Contributions of percolation are evident through the viscoelasticity of condensates and through the formation of heterogeneous distributions of nano- and mesoscale pre-percolation clusters in sub-saturated solutions. Here, we show that clusters formed in sub-saturated solutions of FET (FUS-EWSR1-TAF15) proteins are affected differently by glutamate versus chloride. These differences on the nanoscale, gleaned using a suite of methods deployed across a wide range of protein concentrations, are prevalent and can be unmasked even though the driving forces for phase separation remain unchanged in glutamate versus chloride. Strikingly, differences in anion-mediated interactions that drive clustering saturate on the micron-scale. Beyond this length scale the system separates into coexisting phases. Overall, we find that sequence-encoded interactions, mediated by solution components, make synergistic and distinct contributions to the formation of pre-percolation clusters in sub-saturated solutions, and to the driving forces for phase separation.


Phase Transition , Glutamic Acid/chemistry , Chlorides/chemistry , Humans , Solutions , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/chemistry , Phase Separation
10.
Biomed Pharmacother ; 175: 116723, 2024 Jun.
Article En | MEDLINE | ID: mdl-38723514

The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable advantage of polyene macrolide antibiotic amphotericin B (AmB) which ensures low pathogen resistance is its mechanism of action related to the formation of transmembrane pores in target lipid membranes. Here, we investigated the effects of plant flavones, chrysin, wogonin, baicalein, apigenin, scutellarein, luteolin, morin and fisetin on the pore-forming activity of AmB in the sterol-enriched membranes by electrophysiological assays. Сhrysin, wogonin, baicalein, apigenin, scutellarein, and luteolin were shown to decrease the AmB pore-forming activity in the bilayers composed of palmitoyloleylphosphocholine independently of their sterol composition. Morin and fisetin led to the increase and decrease in the AmB pore-forming activity in the ergosterol- and cholesterol-containing bilayers respectively. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane forming lipids, molecular dynamics simulations, and absorbance spectroscopy revealed the possibility of direct interactions between AmB and some flavones in the water and/or in the lipid bilayer. The influence of these interactions on the antibiotic partitioning between aqueous solution and membrane and/or its transition between different states in the bilayer was discussed.


Amphotericin B , Flavones , Lipid Bilayers , Molecular Dynamics Simulation , Amphotericin B/pharmacology , Amphotericin B/chemistry , Flavones/pharmacology , Flavones/chemistry , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Phase Transition
11.
Biosens Bioelectron ; 259: 116403, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38776802

Robust encapsulation and controllable release of biomolecules have wide biomedical applications ranging from biosensing, drug delivery to information storage. However, conventional biomolecule encapsulation strategies have limitations in complicated operations, optical instability, and difficulty in decapsulation. Here, we report a simple, robust, and solvent-free biomolecule encapsulation strategy based on gallium liquid metal featuring low-temperature phase transition, self-healing, high hermetic sealing, and intrinsic resistance to optical damage. We sandwiched the biomolecules with the solid gallium films followed by low-temperature welding of the films for direct sealing. The gallium can not only protect DNA and enzymes from various physical and chemical damages but also allow the on-demand release of biomolecules by applying vibration to break the liquid gallium. We demonstrated that a DNA-coded image file can be recovered with up to 99.9% sequence retention after an accelerated aging test. We also showed the practical applications of the controllable release of bioreagents in a one-pot RPA-CRISPR/Cas12a reaction for SARS-COV-2 screening with a low detection limit of 10 copies within 40 min. This work may facilitate the development of robust and stimuli-responsive biomolecule capsules by using low-melting metals for biotechnology.


Biosensing Techniques , Phase Transition , SARS-CoV-2 , Biosensing Techniques/methods , SARS-CoV-2/isolation & purification , COVID-19/virology , Gallium/chemistry , Humans , DNA/chemistry , CRISPR-Cas Systems , Capsules/chemistry
12.
Biochim Biophys Acta Biomembr ; 1866(5): 184331, 2024 Jun.
Article En | MEDLINE | ID: mdl-38718958

The causative genes for neurodegenerative polyglutamine (polyQ) diseases produce homopolymeric polyglutamine (polyQ), polyserine (polyS), polyalanine (polyA), polycysteine (polyC), and polyleucine (polyL) sequences by repeat-associated non-AUG (RAN) translation. The cytotoxicity of the intracellular polyQ and RAN products has been extensively investigated. However, little is known about the toxicity of the extracellular polyQ and RAN products on the membranes of viable cells. Because polyQ aggregates induce a deflated morphology of a model membrane, we hypothesized that extracellular polyQ and RAN products might affect the membrane properties of viable cells. In this study, we demonstrated that exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the thermal phase transition behavior of a model membrane composed of a phosphatidylcholine bilayer using differential scanning calorimetry. PolyS fibrils induced morphological changes in viable red blood cells (RBCs). However, both polyS and polyQ non-fibril aggregates had no effects on RBCs. These results highlight the possibility that extracellular fibrils generated from RAN products may alter the properties of neuronal cell membranes, which may contribute to changes in the brain pathology.


Erythrocytes , Liposomes , Peptides , Phosphatidylcholines , Erythrocytes/drug effects , Erythrocytes/metabolism , Phosphatidylcholines/chemistry , Humans , Liposomes/chemistry , Peptides/chemistry , Peptides/pharmacology , Cell Membrane/metabolism , Cell Membrane/drug effects , Cell Membrane/chemistry , Phase Transition , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124462, 2024 Sep 05.
Article En | MEDLINE | ID: mdl-38754204

Membrane fusion is closely related to plasma membrane domains rich in cone-shaped phosphatidylethanolamine (PE) lipids that can reverse membrane curvature under certain conditions. The phase transition of PE-based lipid membranes from the lamellar fluid phase (Lα) to the inverse hexagonal phase (HII) is commonly taken as a general model in reconstructing the membrane fusion pathway, and whose structural features have been mostly described so far using structural and microscopic techniques. The aim of this paper is to decipher the optical and molecular features of Lߠ→ Lα and especially of Lα â†’ HII transition of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipids at pH = 7.0 when they are initially prepared in the form of both multi- and unilamellar liposomes (MLVs and LUVs). The distinction between optical properties of MLS- and LUVs-derived HII phase, provided from turbidity-sensitive temperature-dependent UV-Vis spectra, was attributed to different formation mechanisms of HII phase. Most importantly, from FTIR spectroscopic data of POPE lipids in Lß (15 °C), Lα (50 °C) and HII (85 °C) phases we identified the changes in molecular features of POPE lipids during phase transitions. Among the latter, by far the most significant is different hydration pattern of POPE lipids in MLVs- and LUVs-derived HII phase which extends from the polar-apolar interface all the way to the terminal amino group of the POPE lipid, along with the changes in the conformation of glycerol backbone as evidenced by the signature of α-methylene groups. Molecular dynamics simulations confirmed higher water penetration in HII phase and provided insight into hydrogen bonding patterns.


Phase Transition , Phosphatidylethanolamines , Phosphatidylethanolamines/chemistry , Liposomes/chemistry , Spectroscopy, Fourier Transform Infrared , Spectrophotometry, Ultraviolet , Temperature
14.
Int J Biol Macromol ; 269(Pt 2): 131890, 2024 Jun.
Article En | MEDLINE | ID: mdl-38692534

The rheological and morphological characteristics of Ca-crosslinked alginate hydrogels with two different M/G ratios, α-L-guluronate (G)-rich and ß-D-mannuronate (M)-rich, each with one alginic acid concentration, were investigated. It was found that the stiffness and elasticity of alginate hydrogels are derived from the thickness and density of the fibril network structures. In aqueous alginate solution, ball-like aggregates of alginates are present. Time-resolved small-angle X-ray scattering and time-domain nuclear magnetic resonance measurements suggest that the disaggregation of alginate aggregates and loose fibrillation occur in the early stage of the sol-gel transition. After these induction stage, direct gelation is finally caused by the formation of the egg-box junction. G-rich alginate hydrogel has a higher stiffness and a thicker and denser fibril network structure than M-rich alginate hydrogel. The former also exhibits faster and more significant changes in physical properties during the sol-gel transition.


Alginates , Hydrogels , Phase Transition , Rheology , Alginates/chemistry , Hydrogels/chemistry , Scattering, Small Angle , Hexuronic Acids
15.
Int J Biol Macromol ; 269(Pt 2): 132184, 2024 Jun.
Article En | MEDLINE | ID: mdl-38723814

Phase separation and aggregation behaviour of triton X-100 (TX-100) and bovine serum albumin (BSA) mixture were investigated using cloud point and UV-visible spectroscopic techniques. The effects of various hydrotropes (HYTs) - namely, sodium salicylate (SS), sodium benzoate (SB), glycerol (Glyc), and 4-aminobenzoic acid (4-ABA) - on the cloud point (CP) of TX-100 + BSA were determined. The obtained CP values for the mixed system in the presence of HYTs followed the order: The measured critical micellization concentration (CMC) values of the TX-100 + BSA mixture were found to be significantly altered with varying amounts of BSA. The calculated free energy of clouding and micellization indicated the non-spontaneous nature of the phase transition and the spontaneous association of the TX-100 + BSA mixture. The non-spontaneity of phase separation decreased with increasing concentrations of HYTs. The enumerated values of ∆Hco and ∆Sco were consistently recorded as negative and positive magnitudes, respectively, in all aqueous HYTs media. The clouding process occurred due to a combination of hydrophobic and electrostatic interactions. The binding constant of the mixed system was determined employing the UV-vis spectroscopic method using the Benesi-Hildebrand equation.


Octoxynol , Serum Albumin, Bovine , Spectrophotometry, Ultraviolet , Serum Albumin, Bovine/chemistry , Octoxynol/chemistry , Animals , Cattle , Hydrophobic and Hydrophilic Interactions , Protein Aggregates , Micelles , Phase Transition , Surface-Active Agents/chemistry , Phase Separation
16.
Mol Pharm ; 21(6): 2878-2893, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38767457

Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid-liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug-polymer interactions, are tested against the onset points of the CXB liquid-liquid phase separation (LLPS). It was found that the types of drug-polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB-polymer-water ternary phase diagram was drawn from the findings.


Celecoxib , Polymers , Solubility , Thermodynamics , Water , Polymers/chemistry , Water/chemistry , Celecoxib/chemistry , Kinetics , Chemistry, Pharmaceutical/methods , Phase Transition , Phase Separation
17.
Proc Natl Acad Sci U S A ; 121(23): e2316734121, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38805292

The RNA tailing machinery adds nucleotides to the 3'-end of RNA molecules that are implicated in various biochemical functions, including protein synthesis and RNA stability. Here, we report a role for the RNA tailing machinery as enzymatic modifiers of intracellular amyloidogenesis. A targeted RNA interference screen identified Terminal Nucleotidyl-transferase 4b (TENT4b/Papd5) as an essential participant in the amyloidogenic phase transition of nucleoli into solid-like Amyloid bodies. Full-length-and-mRNA sequencing uncovered starRNA, a class of unusually long untemplated RNA molecules synthesized by TENT4b. StarRNA consists of short rRNA fragments linked to long, linear mixed tails that operate as polyanionic stimulators of amyloidogenesis in cells and in vitro. Ribosomal intergenic spacer noncoding RNA (rIGSRNA) recruit TENT4b in intranucleolar foci to coordinate starRNA synthesis driving their amyloidogenic phase transition. The exoribonuclease RNA Exosome degrades starRNA and functions as a general suppressor of cellular amyloidogenesis. We propose that amyloidogenic phase transition is under tight enzymatic control by the RNA tailing and exosome axis.


Amyloid , Phase Transition , Humans , Amyloid/metabolism , RNA Stability , RNA/metabolism , RNA/genetics , Polyribonucleotide Nucleotidyltransferase/metabolism , Polyribonucleotide Nucleotidyltransferase/genetics
18.
J Phys Chem B ; 128(22): 5397-5406, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38776161

The article correlates between symmetry breaking and phase transition. An analogy, extending from physics to biology, is known to exist between these two topics. Bacteriorhodopsin (bR) as a paradigm of membrane proteins has been used as a case study in the present work. The bR, as the sole protein embedded in what is called a purple membrane (PM), has attracted widespread interest in bionanotechnological applications. The lipids of PM have a crucial role in maintaining the crystal lattice of bR inside PM. For this reason, the present work has been concerned with elucidating the thermal phase transition properties of the PM lipids in orthogonal directions. The results indicated that the axial symmetry of bR exhibits considerable changes occurring at the thermal phase transition of lipids. These changes are brought by an anomaly observed in the time course of orthogonal electric responses during the application of thermal fields on PM. The observed anomaly may bear on symmetry breaking in bR occurring at the phase transition of lipids based on such analogy found between symmetry breaking and phase transition. Lipid-protein interactions may underlie the broken axial symmetry of bR at such lipid thermal transition of PM. Accordingly, thermally perturbed axial symmetry of bR may be of biological relevance relying on the essence of the crystal lattice of bR. Most importantly, a question has to be raised in the present study: Can bR, as a helical protein with broken axial symmetry, affect the symmetry breaking of helical light? This may be of potential technical applications based on a recent discovery that bR breaks the symmetry of helical light.


Bacteriorhodopsins , Phase Transition , Purple Membrane , Bacteriorhodopsins/chemistry , Purple Membrane/chemistry , Purple Membrane/metabolism , Temperature , Halobacterium salinarum/chemistry , Lipids/chemistry
19.
Sci Rep ; 14(1): 8914, 2024 04 17.
Article En | MEDLINE | ID: mdl-38632300

Intracellular aggregation of fused in sarcoma (FUS) is associated with the pathogenesis of familial amyotrophic lateral sclerosis (ALS). Under stress, FUS forms liquid droplets via liquid-liquid phase separation (LLPS). Two types of wild-type FUS LLPS exist in equilibrium: low-pressure LLPS (LP-LLPS) and high-pressure LLPS (HP-LLPS); the former dominates below 2 kbar and the latter over 2 kbar. Although several disease-type FUS variants have been identified, the molecular mechanism underlying accelerated cytoplasmic granule formation in ALS patients remains poorly understood. Herein, we report the reversible formation of the two LLPS states and the irreversible liquid-solid transition, namely droplet aging, of the ALS patient-type FUS variant R495X using fluorescence microscopy and ultraviolet-visible absorption spectroscopy combined with perturbations in pressure and temperature. Liquid-to-solid phase transition was accelerated in the HP-LLPS of R495X than in the wild-type variant; arginine slowed the aging of droplets at atmospheric conditions by inhibiting the formation of HP-LLPS more selectively compared to that of LP-LLPS. Our findings provide new insight into the mechanism by which R495X readily forms cytoplasmic aggregates. Targeting the aberrantly formed liquid droplets (the HP-LLPS state) of proteins with minimal impact on physiological functions could be a novel therapeutic strategy for LLPS-mediated protein diseases.


Amyotrophic Lateral Sclerosis , RNA-Binding Protein FUS , Sarcoma , Humans , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/pathology , Phase Transition , RNA-Binding Protein FUS/genetics , RNA-Binding Protein FUS/metabolism
20.
Int J Biol Macromol ; 268(Pt 2): 131735, 2024 May.
Article En | MEDLINE | ID: mdl-38653424

The CMC-PNIPAM hydrogel with semi-interpenetrating structure and temperature-sensitivity was prepared by in-situ polymerization of N-isopropylacrylamide (NIPAM) in sodium carboxymethylcellulose (CMC) solution at room temperature. The mass ratio of CMC to NIPAM was a key factor influencing the network structure and property of CMC-PNIPAM hydrogel. The low critical phase transition temperature (LCST) of CMC-PNIPAM hydrogels increased from 34.4 °C to 35.8 °C with the mass ratio of CMC to NIPAM rising from 0 to 1.2. The maximum compressive stress of CMC-PNIPAM hydrogel reached to 26.7 kPa and the relaxation elasticity was 52 % at strain of 60 %. The viscoelasticity of CMC-PNIPAM hydrogel was consistent with the generalized Maxwell model. The maximum swelling ratio in deionized water was 170.25 g·g-1 (dried hydrogel) with swelling rate of 2.57 g·g-1·min-1 at 25 °C. CMC-PNIPAM hydrogel hardly absorbed water above LCST, but the swollen hydrogel could release water at the rate of 0.36 g·g-1·min-1 once exceeding LCST. The test of water retention showed that soil mixed with 2 wt% dried CMC-PNIPAM hydrogel could retain 13.08 wt% water after 30 days at 25 °C that was 4.4 times than that of controlled soil without CMC-PNIPAM hydrogel. The semi-interpenetrating CMC-PNIPAM hydrogel showed a potential to conserve water responding to temperature.


Acrylic Resins , Carboxymethylcellulose Sodium , Hydrogels , Temperature , Water , Acrylic Resins/chemistry , Water/chemistry , Hydrogels/chemistry , Carboxymethylcellulose Sodium/chemistry , Phase Transition , Viscosity , Acrylamides/chemistry
...