scholarly journals Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions

2018 ◽  
Author(s):  
Yanxian Lin ◽  
James McCarty ◽  
Jennifer N. Rauch ◽  
Kris T. Delaney ◽  
Kenneth S. Kosik ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Electrostatic Interactions ◽  
Driving Forces ◽  
Polymer Concentration ◽  
Equilibrium Phase ◽  
Charge Ratio ◽  
Solution Temperature ◽  
Complex Coacervation ◽  
Experimental Conditions ◽  
Form Complex

AbstractThe conditions that lead to the liquid-liquid phase separation (LLPS) of the tau protein, a microtubule associated protein whose pathological aggregation has been implicated in neurodegenerative disorders, are not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding its LLPS. Using a combination of EPR, turbidity measurements, and microscopy, we show that tau and RNA form complex coacervates with lower critical solution temperature (LCST) behavior. The coacervates are reversible, and the biopolymers can be driven to the supernatant phase or coacervate phase by varying the experimental conditions (temperature, salt concentration, tau:RNA charge ratio, total polymer concentration and osmotic stress). Furthermore, the coacervates can be driven to a fibrillar state through the addition of heparin. The equilibrium phase diagram of the tau/RNA complex coacervate system can be described by a Flory-Huggins model, augmented by an approximate Voorn Overbeek electrostatic term (FH-VO), after fitting the experimental data to an empirical Flory interaction parameter divided into an entropic and enthalpic term. However, a more advanced model in which tau and RNA are treated as discrete bead-spring chains with a temperature-dependent excluded volume interaction and electrostatic interactions between charged residues, investigated through field theoretic simulations (FTS), provided direct and unique insight into the thermodynamic driving forces of tau/RNA complexation. FTS corroborated the experimental finding that the complex coacervation of tau and RNA is has an entropy-driven contribution, with a transition temperature around the physiological temperature of 37 °C and salt concentrations around 100-150 mM. Together, experiment and simulation show that LLPS of tau can occur under physiological cellular conditions, but has a narrow equilibrium window over experimentally tunable parameters including temperature, salt and tau concentrations. Guided by our phase diagram, we show that tau can be driven towards LLPS under live cell coculturing conditions with rationally chosen experimental parameters.

scholarly journals Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yanxian Lin ◽  
James McCarty ◽  
Jennifer N Rauch ◽  
Kris T Delaney ◽  
Kenneth S Kosik ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Driving Forces ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram ◽  
Complex Coacervation ◽  
Form Complex ◽  
Experimental Parameters ◽  
Advanced Model ◽  
Insight Into ◽  
Liquid Liquid Phase Separation

The mechanism that leads to liquid-liquid phase separation (LLPS) of the tau protein, whose pathological aggregation is implicated in neurodegenerative disorders, is not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding whether LLPS is an equilibrium or intermediate state. We demonstrate that tau and RNA reversibly form complex coacervates. While the equilibrium phase diagram can be fit to an analytical theory, a more advanced model is investigated through field theoretic simulations (FTS) that provided direct insight into the thermodynamic driving forces of tau LLPS. Together, experiment and simulation reveal that tau-RNA LLPS is stable within a narrow equilibrium window near physiological conditions over experimentally tunable parameters including temperature, salt and tau concentrations, and is entropy-driven. Guided by our phase diagram, we show that tau can be driven toward LLPS under live cell coculturing conditions with rationally chosen experimental parameters.

scholarly journals Upper Critical Solution Temperature (UCST) Behavior of Coacervate of Cationic Protamine and Multivalent Anions

Polymers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 691 ◽  
Author(s):  
Hyungbin Kim ◽  
Byoung-jin Jeon ◽  
Sangsik Kim ◽  
YongSeok Jho ◽  
Dong Soo Hwang
Keyword(s):  
Electrostatic Interactions ◽  
Solution Temperature ◽  
Complex Coacervation ◽  
Critical Factors ◽  
Critical Solution Temperature ◽  
Temperature Changes ◽  
Upper Critical Solution Temperature ◽  
Large Asymmetry ◽  
Positively Charged ◽  
Liquid Liquid Phase Separation

Complex coacervation is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells. Yet while one of the critical factors for complex coacervation is temperature, little analysis and research has been devoted to the temperature effect on complex coacervation. Here, we performed a complex coacervation of cationic protamine and multivalent anions (citrate and tripolyphosphate (TPP)). Both mixtures (i.e., protamine/citrate and protamine/TPP) underwent coacervation in an aqueous solution, while a mixture of protamine and sodium chloride did not. Interestingly, the complex coacervation of protamine and multivalent anions showed upper critical solution temperature (UCST) behavior, and the coacervation of protamine and multivalent anions was reversible with solution temperature changes. The large asymmetry in molecular weight between positively charged protamine (~4 kDa) and the multivalent anions (<0.4 kDa) and strong electrostatic interactions between positively charged guanidine residues in protamine and multivalent anions were likely to contribute to UCST behavior in this coacervation system.

scholarly journals Equilibrium phase diagram and thermal responses of charged DNA-virus rod-suspensions at low ionic strengths

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyongok Kang
Keyword(s):  
Phase Diagram ◽  
Ionic Strength ◽  
Electrostatic Interactions ◽  
Second Harmonic ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram ◽  
Time Correlation ◽  
Debye Screening Length ◽  
High Concentration ◽  
Scanning Calorimetry

AbstractThe collective behavior of DNA is important for exploring new types of bacteria in the means of detection, which is greatly interested in the understanding of interactions between DNAs in living systems. How they self-organize themselves is a physical common phenomenon for broad ranges of thermodynamic systems. In this work, the equilibrium phase diagrams of charged chiral rods (fd viruses) at low ionic strengths (below a few mM) are provided to demonstrate both replicas of (or self-organized) twist orders and replica symmetry breaking near high concentration glass-states. By varying the ionic strengths, it appears that a critical ionic strength is obtained below 1–2 mM salt, where the twist and freezing of nematic domains diverge. Also, the microscopic relaxation is revealed by the ionic strength-dependent effective Debye screening length. At a fixed low ionic strength, the local orientations of twist are shown by two different length scales of optical pitch, in the chiral-nematic N* phase and the helical domains $$H_{D}$$ H D , for low and high concentration, respectively. RSB occurs in several cases of crossing phase boundary lines in the equilibrium phase diagram of DNA-rod concentration and ionic strength, including long-time kinetic arrests in the presence of twist orders. The different pathways of PATH I, II and III are due to many-body effects of randomized orientations for charged fd rods undergoing long-range electrostatic interactions in bulk elastic medium. In addition, the thermal stability are shown for chiral pitches of the N* phase and the abnormal cooling process of a specific heat in a structural glass. Here, the concentration-driven twist-effects of charged DNA rods are explored using various experimental methods involving image-time correlation, microscopic dynamics in small angle dynamic light scattering, optical activity in second harmonic generation, and differential scanning calorimetry for the glass state.

Intermetallic Formation in the Aluminum–Copper System

2003 ◽  
Vol 10 (04) ◽  
pp. 677-683 ◽  
Author(s):  
E. B. Hannech ◽  
N. Lamoudi ◽  
N. Benslim ◽  
B. Makhloufi
Keyword(s):  
Electron Microscopy ◽  
Phase Diagram ◽  
Solid Solution ◽  
Intermetallic Layer ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram ◽  
Diffusion Couples ◽  
Intermetallic Formation ◽  
Parabolic Law ◽  
Scanning Electron

Intermetallic formation at 425°C in the aluminum–copper system has been studied by scanning electron microscopy using welded diffusion couples. Several Al–Cu phases predicted by the equilibrium phase diagram of the elements and voids taking place in the diffusion zone have been detected in the couples. The predominant phases were found to be Al 2 Cu 3 and the solid solution of Al in Cu, α. The growth of the intermetallic layer obeyed the parabolic law.

scholarly journals The development of low-temperature heat-treatable high-pressure die-cast Al–Mg–Fe–Mn alloys with Zn

2021 ◽  
Author(s):  
Xiangzhen Zhu ◽  
Fuchu Liu ◽  
Shihao Wang ◽  
Shouxun Ji
Keyword(s):  
Heat Treatment ◽  
Low Temperature ◽  
Mechanical Test ◽  
Equilibrium Phase ◽  
Solution Temperature ◽  
Tem Analysis ◽  
Die Cast ◽  
Zn Concentration ◽  
Temperature Heat ◽  
Cast Alloys

AbstractIn the present work, a novel low-temperature heat-treatable recycled die-cast Al–Mg alloy was developed by adding Zn into non-heat-treatable Al–5Mg–1.5Fe–0.5Mn alloy. The results showed that Zn additions resulted in the formation of equilibrium phase T-Mg32(Al, Zn)49 under as-cast condition, which can be dissolved into the α-Al matrix at a relatively low solution temperature (430 °C) and thus set the base for the low-temperature heat treatment. The mechanical test results indicated that Zn additions had a smooth liner improvement in the strength of all as-cast alloys and T6-state alloys with 1% and 2% Zn as its concentration increased but resulted in a sharp improvement on the strength of T6-state alloy when Zn concentration increased from 2 to 3%. TEM analysis revealed that the precipitate in T6-state Al–5Mg–1.5Fe–0.5Mn–3Zn alloy is η′ phase, rather than the widely reported T″ or T′ phase in other Al–Mg–Zn alloys with approximately same Mg and Zn concentrations. After the optimized low-temperature T6 heat treatment (solution at 430 °C for 60 min and ageing at 120 °C for 16 h), the Al–5Mg–1.5Fe–0.5Mn–3Zn alloy exhibits the yield strength of 321 MPa, ultimate tensile strength of 445 MPa and elongation of 6.2%.

Equilibrium phase diagram of polystyrene and 8CB

1999 ◽  
Vol 37 (15) ◽  
pp. 1841-1848 ◽  
Author(s):  
Farida Benmouna ◽  
Abdelylah Daoudi ◽  
Fr�d�rick Roussel ◽  
Jean-Marc Buisine ◽  
Xavier Coqueret ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram

The physicochemical and DNA binding studies of some medicinal compounds in solutions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abbas Khan ◽  
Naila ◽  
Muhammad Humayun ◽  
Muhammad Sufaid Khan ◽  
Luqman Ali Shah ◽  
...  
Keyword(s):  
Flow Behavior ◽  
Aqueous Media ◽  
Research Work ◽  
Binding Constants ◽  
Physicochemical Study ◽  
Solution Temperature ◽  
Binding Studies ◽  
Experimental Conditions ◽  
Medicinal Compounds ◽  
Association Behavior

Abstract To understand the expected mode of action, the physicochemical study on the solution properties of medicinal compounds and their interaction with deoxyribonucleic acid (DNA), under varying experimental conditions, is of prime importance. The present research work illustrates the physicochemical study and interaction of certain medicinal compounds such as; Levofloxacin, Ciprofloxacin, and Ibuprofen with DNA. Density, viscosity and surface tension measurements have been performed in order to determine, in a systematic manner, the physicochemical, volumetric and thermodynamic properties of these compounds; and most of these parameters have shown different behavior with varying concentration of solution, temperature of the medium and chemical nature/structure of the compound. In addition, these drugs showed a spontaneous surface-active and association behavior in aqueous solutions. The flow behavior, surface properties, volumetric behavior and solute–solvent interaction of these drugs were prominently influenced by experimental variables and addition of DNA to their solutions. UV–Visible spectroscopy was also used to examine the interaction of these drugs with DNA in aqueous media in detail. Calculated values of binding constants (Kb) for all complexes of drug-DNA are positive, indicating a fruitful binding process. It is seen that a smaller Kb value reflects weaker binding of the drug with DNA and vise versa. Due to the difference in the chemical structure of drugs the values of binding constant are different for various drug-DNA complexes and follow the order Kb(Levofloxacin-DNA) > Kb(Ciprofloxacin-DNA) > Kb(Ibuprofen-DNA). On the basis of spectral changes and Kb it can be said that the binding of all these drugs with DNA may be of physicochemical nature and the dominating binding force be of hydrogen bonding between oxygen of drugs and hydrogen of DNA units and the drug having more oxygen atoms showed stronger binding ability. The data further suggest a limited possibility of chemical type attachment of these drugs with DNA.

scholarly journals Formation of Intermediate Phases and Supersaturated Solid Solution in Al-Cu System during Diffusion

2018 ◽  
Vol 383 ◽  
pp. 31-35 ◽  
Author(s):  
Alexey Rodin ◽  
Nataliya Goreslavets
Keyword(s):  
Phase Diagram ◽  
Solid Solution ◽  
High Temperature ◽  
Chemical Composition ◽  
Low Temperature ◽  
Supersaturated Solid Solution ◽  
Diffusion Processes ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram ◽  
Intermediate Phases

The study of diffusion processes in the aluminum - copper system was carried out at the temperature 350 and 520 °C. Special attention was paid on the chemical composition of the system near Al/Cu interface. It was determined that the intermediate phases in the system, corresponding to the equilibrium phase diagram, were not formed at low temperature. At high temperature the intermediate phases forms starting with Cu - rich phases. In both cases supersaturated solid solution of copper in aluminum could be observed near the interface.

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