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Article
Biophysics
Audrey Cochard et al.
Summary: This study presents a method to form RNA-containing condensates in living cells. Programmable tools are used to recruit a specific RNA species and control the formation and dissolution of condensates. The recruitment of RNA changes the material properties of condensates, and the size of condensates scales with RNA surface density.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Dushyant Kumar Garg et al.
Summary: TAR DNA-binding protein 43 (TDP-43) regulates cellular functions through liquid-liquid phase separation (LLPS), which is mediated by its C-terminal low-complexity domain (TDP43-LCD). Pathological inclusions of TDP-43, found in neurodegenerative disorders, are rich in C-terminal fragments. Understanding the assembly process of TDP43-LCD is crucial for both functional liquid-like assemblies and pathological aggregates.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Andrew P. Latham et al.
Summary: Multi-component phase separation is a key mechanism for the formation of biological condensates. The stability of these condensates depends on the protein-DNA mixing ratio, as revealed in the study. A layered organization in condensates formed by mixing HP1, histone H1, and DNA was observed, providing insights into cooperative DNA packaging between chromatin regulators.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Anukool A. Bhopatkar et al.
Summary: Cytoplasmic inclusions of aberrant proteolytic fragments of TDP-43 are associated with FTLD, and the effects of cysteine-rich granulins (GRNs) on TDP-43 may involve liquid-liquid phase separation (LLPS) driven by negative charges.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Marco Ancona et al.
Summary: Through simulations, we studied the interplay between protein-protein and protein-chromatin interactions, revealing different mechanisms and characteristics of condensate formation under various conditions. Particularly, the density of protein droplets varies with the overall protein concentration when interacting with chromatin.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Srivastav Ranganathan et al.
Summary: This study investigates the physical basis of structural diversity in condensed phases of multi-domain RNA-binding proteins using simulations. The results reveal a highly cooperative first-order transition between disordered structures and an ordered phase, as well as the impact of homodomain and heterodomain interactions on the variety of structures.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Tanja Mittag et al.
Summary: Macromolecular phase separation plays an important role in the spatial organization within cells. By understanding the synergy between networking and density transitions, we can explain the process of phase separation coupled to percolation (PSCP). This process forms viscoelastic network fluids with specific internal network structures, allowing for time-dependent interactions between viscous and elastic properties. PSCP provides insights into the role of macromolecular phase separation in biology by connecting different observations and addressing related challenges.
Article
Biochemistry & Molecular Biology
Henry R. Kilgore et al.
Summary: Biomolecular condensates compartmentalize and regulate assemblies of biomolecules, and understanding their chemical properties can help to design drugs with improved efficacy and reduced toxicity.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biophysics
David De Sancho
Summary: Macromolecular phase separation plays a crucial role in the formation of membraneless organelles and cellular organization. The formation of condensate-spanning networks in protein solutions is determined by the interplay between two classes of residues, stickers and spacers, with multivalency and sequence patterning being the main determinants for phase separation. Atomistic molecular dynamics simulations demonstrate that ternary amino acid mixtures involving both sticker and spacer types can undergo phase separation, resulting in phases with intermediate compaction and greater fluidity compared to sticker-only condensates.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
N. Amy Yewdall et al.
Summary: Cellular condensates are heterogeneous mixtures of proteins and RNA formed in complex environments, and the material properties and composition of the condensates can be influenced by ATP:Mg2+. ATP can reverse the gel-like structures formed by RNA alone and enhance the partitioning of certain components, while Mg2+ concentrations slow down the dynamics of RNA and lead to the formation of gel-like states.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Yutaka Murata et al.
Summary: Liquid-liquid phase separation (LLPS) has been widely studied in recent years for explaining the formation of cellular biomolecular condensates. Molecular simulation methods, such as the stoichiometric interaction (SI) potential, have been used to gain insights into the structures of these complex components. However, the SI potential alone cannot quantitatively reproduce the phase diagram of LLPS, and the combination of SI and pairwise interactions is necessary. Biomolecular condensates with mixed SI and pairwise interactions exhibit fluidity, while those with pairwise interactions alone do not show detectable diffusion. The phase diagrams obtained from simulations using different numbers of tandem domains agree quantitatively with experimental results.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
SoRi Jang et al.
Summary: This study systematically examined the dynamic subcellular localization of glycolytic protein phospho-fructokinase-1/PFK-1.1 in Caenorhabditis elegans, showing that PFK-1.1 can form condensates near synapses in neurons in response to energy stress and exhibit liquid-like properties. The findings suggest that PFK-1.1 condensates may represent novel metabolic subcompartments.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Kulveer Singh et al.
Summary: In this study, a model of intrinsically disordered proteins (IDPs) as associative polymers in poor solvent was proposed, exploring the internal morphology dependence on the primary structure of IDPs. It was observed that the location of stickers along the chain contour can lead to changes in the shape, size, and number of sticker clusters inside liquid droplets. Aging phenomenon was also observed in droplets of associative polymers.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Jean K. Chung et al.
Summary: Lipid miscibility phase separation and protein condensation phase transitions are important organizational principles in cells. By reconstituting LAT:Grb2:SOS protein condensation on giant unilamellar vesicles, it is shown that the assembly of protein condensates can drive lipid phase separation. This process is controlled by tyrosine phosphorylation on LAT and leads to the localization of downstream signaling molecules into the protein condensates.
BIOPHYSICAL JOURNAL
(2021)
Review
Cell Biology
Christine Roden et al.
Summary: Recent studies have shown the significant contribution of RNA to cellular liquid-liquid phase separation and condensate formation, which play important roles in various cellular functions such as RNA transport, supporting catalytic processes, and stress responses. Although RNA and RNA-protein condensates are important in cells, the role of RNA in liquid-liquid phase separation has received less attention in comparison to RNA-binding proteins.Properties such as composition, length, structure, modifications, and expression levels of RNA can modulate the biophysical features of native condensates, influencing their size, shape, viscosity, and composition. RNA-protein condensates are involved in various cellular functions, including cell compartmentalization through RNA transport and localization, supporting catalytic processes, storage and inheritance of specific molecules, as well as buffering noise and responding to stress.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Biophysics
Rabia Laghmach et al.
Summary: The genetic material of eukaryotes is segregated into euchromatin for active transcription and heterochromatin for silent compartments, with the spatial arrangement evolving over cellular life resembling active multiphase liquids. Nuclear imaging experiments reveal dynamical signatures of chromatin such as viscoelastic responses and liquid-liquid phase separation, which are driven by interactions between chromatin types. A field-theoretic model and simulations of liquid chromatin behavior in the nucleus provide insights into the dynamics and patterning of chromatin, including the emergence of mesoscale chromatin channels and droplets. Interactions between heterochromatin and lamina enhance euchromatin mobility and introduce correlated motions of heterochromatin droplets.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Giacomo Bartolucci et al.
Summary: Phase separation and transitions among different molecular states in living cells are driven by local equilibrium thermodynamics or active processes controlled by biological fuel. The behavior of phase-separating systems with molecular transitions differs between thermodynamic equilibrium and cases where detailed balance of molecular transition rates is broken by fuel presence. Quasi-discontinuous changes in droplet composition can occur by breaking detailed balance of molecular transition, providing a versatile mechanism to control properties of intracellular and synthetic condensates.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Andres R. Tejedor et al.
Summary: This study used a chemically-accurate coarse-grained model to investigate the impact of RNA on the properties of biomolecular condensates, revealing a complex regulatory role of RNA on condensate stability and transport properties. At low RNA concentrations, RNA can enhance phase separation of proteins, while at high concentrations, it inhibits protein self-assembly.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Fernando Muzzopappa et al.
Summary: Living organisms typically store their genomic DNA in a condensed form driven by factors such as macromolecular crowding, multivalent cations, or positively charged proteins. The condensation of DNA can lead to distinct morphologies and phase separation into DNA-dilute and DNA-dense phases. DNA length plays a critical role in determining the fluidity of DNA condensates, with short DNA molecules forming liquid-like assemblies and longer DNA molecules forming solid-like assemblies.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Jerelle A. Joseph et al.
Summary: The study shows that RNA enhances the stability of protein-RNA mixtures by increasing molecular connectivity of proteins, accelerating the nucleation stage of phase separation, and controlling spatial segregation within condensates through adjusting interaction strengths and stoichiometries.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Willem Kasper Spoelstra et al.
Summary: This study presents a label-free detection method for specific nucleic acid sequences based on solution turbidity caused by liquid-liquid phase separation (LLPS). The detection of specific sequences can be observed with the naked eye, providing a simple and low-cost alternative for molecular diagnostics.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Raymond F. Berkeley et al.
Summary: Proteins found in pathological fibrils can exhibit liquid-liquid phase separation tendencies, with real-time tracking revealing structural transitions in RNA-binding protein FUS. Disease-relevant mutations have significant effects on the process.
BIOPHYSICAL JOURNAL
(2021)
Review
Cell Biology
Simon Alberti et al.
Summary: Biomolecular condensates, formed through liquid-liquid phase separation in a tightly regulated manner, have fundamental roles in cellular organization and physiology. Recent studies provide insights into how cellular stress, ageing-related loss of homeostasis, and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensates.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Biophysics
Jonas Ahlers et al.
Summary: Liquid-liquid phase separation (LLPS) is a fundamental process in cell biology, where proteins form condensates to regulate cellular processes. This study provides experimental evidence for the role of solvent as a thermodynamic driving force in LLPS, with both protein-protein interactions and release of hydration water playing important roles. Understanding these driving forces can contribute to insights into biomolecular condensation and neurodegenerative diseases.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Jocelyn C. Newton et al.
Summary: L1 element autonomously replicates in the human genome, causing DNA damage and genomic instability. Activation of L1 triggers interferon response and age-associated inflammation. ORF1 protein forms liquid droplets in a salt-dependent manner, with interactions between its N-terminal and coiled-coil domain being necessary for phase separation.
BIOPHYSICAL JOURNAL
(2021)
Article
Cell Biology
Monika Fuxreiter et al.
Summary: Proteins undergoing liquid-liquid phase separation are being discovered more frequently, with the liquid condensed state considered a fundamental state of proteins, playing various biological functions.
NATURE CELL BIOLOGY
(2021)
Review
Cell Biology
Andrew S. Lyon et al.
Summary: Biomolecular condensates are membraneless molecular assemblies formed via liquid-liquid phase separation, playing important roles in controlling biochemical reactions and regulating cell organization and function throughout eukaryotic cells.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Erik W. Martin et al.
Article
Biochemistry & Molecular Biology
David W. Sanders et al.
Article
Multidisciplinary Sciences
Joshua A. Riback et al.
Article
Biochemistry & Molecular Biology
Vladimir N. Uversky
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2017)
Review
Biochemistry & Molecular Biology
Jerson L. Silva et al.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
