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 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.

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.

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

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.

scholarly journals Equilibrium Phase Diagram of the Zn–Ag Alloy

2018 ◽  
Vol 20 (3) ◽  
pp. 72-84
Author(s):  
Alexey Korolev ◽  
◽  
Gennagy Maltsev ◽  
Konstantin Timofeev ◽  
Vladimir Lobanov ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram

Equilibrium Phase Diagram of Li＋,Na＋∥,CO32－,B4O72－-H2O Quaternary System at 288 K

2002 ◽  
Vol 18 (09) ◽  
pp. 835-837 ◽  
Author(s):  
Sang Shi-Hua ◽  
◽  
Yin Hui-An ◽  
Tang Ming-Lin ◽  
Zhang Yun-Xiang
Keyword(s):  
Phase Diagram ◽  
Quaternary System ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram

The equilibrium phase diagram of the magnesium–copper–yttrium system

2008 ◽  
Vol 40 (7) ◽  
pp. 1064-1076 ◽  
Author(s):  
Mohammad Mezbahul-Islam ◽  
Dmytro Kevorkov ◽  
Mamoun Medraj
Keyword(s):  
Phase Diagram ◽  
Equilibrium Phase ◽  
Equilibrium Phase Diagram
Sign in / Sign up

Export Citation Format

Share Document