Phase behavior of lysozyme solutions in the liquid–liquid phase coexistence region at high hydrostatic pressures

2016 ◽  
Vol 18 (21) ◽  
pp. 14252-14256 ◽  
Author(s):  
Julian Schulze ◽  
Johannes Möller ◽  
Jonathan Weine ◽  
Karin Julius ◽  
Nico König ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
High Pressures ◽  
Phase Coexistence ◽  
Protein Solutions ◽  
Separation Region ◽  
Coexistence Region ◽  
High Hydrostatic Pressures ◽  
Liquid Liquid Phase Separation

Dense protein solutions exhibit a reentrant liquid–liquid phase separation region at high pressures.

scholarly journals Kinetics of liquid–liquid phase separation in protein solutions exhibiting LCST phase behavior studied by time-resolved USAXS and VSANS

Soft Matter ◽  
2016 ◽  
Vol 12 (46) ◽  
pp. 9334-9341 ◽  
Author(s):  
Stefano Da Vela ◽  
Michal K. Braun ◽  
Andreas Dörr ◽  
Alessandro Greco ◽  
Johannes Möller ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
Liquid Phase Separation ◽  
Protein Solutions ◽  
Time Resolved ◽  
Kinetics Of ◽  
Liquid Liquid Phase Separation

Charge-controlled metastable liquid–liquid phase separation in protein solutions as a universal pathway towards crystallization

Soft Matter ◽  
2012 ◽  
Vol 8 (5) ◽  
pp. 1313-1316 ◽  
Author(s):  
Fajun Zhang ◽  
Roland Roth ◽  
Marcell Wolf ◽  
Felix Roosen-Runge ◽  
Maximilian W. A. Skoda ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Protein Solutions ◽  
Metastable Liquid ◽  
Liquid Liquid Phase Separation

scholarly journals Phase behavior of the polymer/drug system PLA/DEET: Effect of PLA molar mass on subambient liquid-liquid phase separation

2018 ◽  
Vol 660 ◽  
pp. 77-81 ◽  
Author(s):  
Chanita Sungkapreecha ◽  
Mark J. Beily ◽  
Jörg Kressler ◽  
Walter W. Focke ◽  
René Androsch
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
Molar Mass ◽  
Liquid Phase Separation ◽  
Liquid Liquid Phase Separation

scholarly journals Dipeptides are minimalistic but sufficient for liquid-liquid phase separation

2021 ◽  
Author(s):  
Yiming Tang ◽  
Santu Bera ◽  
Yifei Yao ◽  
Jiyuan Zeng ◽  
Zenghui Lao ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
General Property ◽  
Md Simulations ◽  
Building Blocks ◽  
Liquid Phase Separation ◽  
Sequence Length ◽  
Multivalent Interactions ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation (LLPS) of proteins mediates the assembly of biomolecular condensates involved in physiological and pathological processes. Identifying the minimalistic building blocks and the sequence determinant of protein phase separation is of urgent importance but remains challenging due to the enormous sequence space and difficulties of existing methodologies in characterizing the phase behavior of ultrashort peptides. Here we demonstrate computational tools to efficiently quantify the microscopic fluidity and density of liquid-condensates/solid-aggregates and the temperature-dependent phase diagram of peptides. Utilizing our approaches, we comprehensively predict the LLPS abilities of all 400 dipeptide combinations of coded amino acids based on 492 micro-second molecular dynamics simulations, and observe the occurrences of spontaneous LLPS. We identify 54 dipeptides that form solid-like aggregates and three categories of dipeptides with high LLPS propensity. Our predictions are validated by turbidity assays and differential interference contrast (DIC) microscopy on four representative dipeptides (WW, QW, GF, and VI). Phase coexistence diagrams are constructed to explore the temperature dependence of LLPS. Our results reveal that aromatic moieties are crucial for a dipeptide to undergo LLPS, and hydrophobic and polar components are indispensable. We demonstrate for the first time that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, suggesting that LLPS is a general property of peptides/proteins, independent of their sequence length. This study provides a computational and experimental approach to the prediction and characterization of the phase behavior of minimalistic peptides, and will be helpful for understanding the sequence-dependence and molecular mechanism of protein phase separation.SignificanceProtein liquid-liquid phase separation (LLPS) is associated with human health and diseases. Identifying the minimalistic building blocks and sequence determinants of LLPS is of urgent importance but remains computationally challenging partially due to the lack of methodologies characterizing the liquid condensates. Herein we provide approaches to evaluate LLPS ability of dipeptides, and screen all 400 dipeptides by MD simulations combined with multi-bead-per-residue models which capture key interactions driving LLPS that are missing in one-bead-per-residue models. Three categories of LLPS dipeptides are identified and the experimentally-verified QW dipeptide is by far the smallest LLPS system. Our results suggest that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, and LLPS is a general property of peptides/proteins, independent of their length.

An intrinsically disordered pathological prion variant Y145Stop converts into self-seeding amyloids via liquid–liquid phase separation

2021 ◽  
Vol 118 (45) ◽  
pp. e2100968118
Author(s):  
Aishwarya Agarwal ◽  
Sandeep K. Rai ◽  
Anamika Avni ◽  
Samrat Mukhopadhyay
Keyword(s):  
Phase Transitions ◽  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
Intrinsically Disordered Proteins ◽  
Liquid Phase Separation ◽  
Disordered Proteins ◽  
Cell Physiology ◽  
Intrinsically Disordered ◽  
Liquid Liquid Phase Separation

Biomolecular condensation via liquid–liquid phase separation of intrinsically disordered proteins/regions (IDPs/IDRs) along with other biomolecules is proposed to control critical cellular functions, whereas aberrant phase transitions are associated with a range of neurodegenerative diseases. Here, we show that a disease-associated stop codon mutation of the prion protein (PrP) at tyrosine 145 (Y145Stop), resulting in a truncated, highly disordered, N-terminal IDR, spontaneously phase-separates into dynamic liquid-like droplets. Phase separation of this highly positively charged N-terminal segment is promoted by the electrostatic screening and a multitude of weak, transient, multivalent, intermolecular interactions. Single-droplet Raman measurements, in conjunction with an array of bioinformatic, spectroscopic, microscopic, and mutagenesis studies, revealed a highly mobile internal organization within the liquid-like condensates. The phase behavior of Y145Stop is modulated by RNA. Lower RNA:protein ratios promote condensation at a low micromolar protein concentration under physiological conditions. At higher concentrations of RNA, phase separation is abolished. Upon aging, these highly dynamic liquid-like droplets gradually transform into ordered, β-rich, amyloid-like aggregates. These aggregates formed via phase transitions display an autocatalytic self-templating characteristic involving the recruitment and binding-induced conformational conversion of monomeric Y145Stop into amyloid fibrils. In contrast to this intrinsically disordered truncated variant, the wild-type full-length PrP exhibits a much lower propensity for both condensation and maturation into amyloids, hinting at a possible protective role of the C-terminal domain. Such an interplay of molecular factors in modulating the protein phase behavior might have much broader implications in cell physiology and disease.

Reentrant condensation, liquid–liquid phase separation and crystallization in protein solutions induced by multivalent metal ions

2014 ◽  
Vol 86 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Fajun Zhang ◽  
Felix Roosen-Runge ◽  
Andrea Sauter ◽  
Marcell Wolf ◽  
Robert M. J. Jacobs ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Metal Ions ◽  
Protein Interactions ◽  
Protein Crystallization ◽  
Liquid Phase Separation ◽  
Protein Solutions ◽  
Metastable Liquid ◽  
Multivalent Metal ◽  
Liquid Liquid Phase Separation

Abstract We briefly summarize the recent progress in tuning protein interactions as well as phase behavior in protein solutions using multivalent metal ions. We focus on the influence of control parameters and the mechanism of reentrant condensation, the metastable liquid–liquid phase separation and classical vs. non-classical pathways of protein crystallization.

Temperature-dependent Reentrant Phase Transition of RNA-polycation Mixtures

Soft Matter ◽  
2022 ◽  
Author(s):  
Paul Pullara ◽  
Ibraheem Alshareedah ◽  
Priya Banerjee
Keyword(s):  
Phase Transition ◽  
Phase Separation ◽  
Liquid Phase ◽  
Phase Behavior ◽  
Soft Matter ◽  
Biological Systems ◽  
Liquid Phase Separation ◽  
Temperature Dependent ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation (LLPS) of multivalent biopolymers is a ubiquitous process in biological systems and is of importance in bio-mimetic soft matter design. The phase behavior of biomolecules, such as...

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