Phase Transitions in Chemically Fueled, Multiphase Complex Coacervate Droplets DOI Creative Commons

Carsten Donau,

Fabian Späth, Michele Stasi

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 6, 2022

Abstract Membraneless organelles are droplets in the cytosol that regulated by chemical reactions. Increasing studies suggest they internally organized. However, how these subcompartments remains elusive. Herein, we describe a complex coacervate‐based model composed of two polyanions and short peptide. With reaction cycle, control affinity peptide for polyelectrolytes leading to distinct regimes inside phase diagram. We study transitions from one regime another identify new can only occur under kinetic control. Finally, show cycle controls liquidity offering insights into active processes cells play an important role tuning liquid state membraneless organelles. Our work demonstrates not thermodynamic properties but also kinetics should be considered organization multiple phases droplets.

Language: Английский

RNA-Mediated Feedback Control of Transcriptional Condensates DOI Creative Commons
Jonathan E. Henninger, Ozgur Oksuz, Krishna Shrinivas

et al.

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 207 - 225.e24

Published: Dec. 16, 2020

Language: Английский

Citations

453
Peptide-based coacervates as biomimetic protocells DOI Creative Commons
Manzar Abbas, Wojciech P. Lipiński, Jiahua Wang

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(6), P. 3690 - 3705

Published: Jan. 1, 2021

This tutorial review describes molecular design principles for peptides and peptide derivatives undergoing phase separation highlights the potential of resulting coacervate protocells.

Language: Английский

Citations

326
Multiphase Complex Coacervate Droplets DOI Creative Commons
Tiemei Lu, Evan Spruijt

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(6), P. 2905 - 2914

Published: Jan. 20, 2020

Liquid–liquid phase separation plays an important role in cellular organization. Many subcellular condensed bodies are hierarchically organized into multiple coexisting domains or layers. However, our molecular understanding of the assembly and internal organization these multicomponent droplets is still incomplete, rules for coexistence phases lacking. Here, we show that formation multiphase with up to three layers a generic phenomenon mixtures complex coacervates, which serve as models charge-driven liquid–liquid separated systems. We present simple theoretical guidelines explain both hierarchical arrangement demixing transition using interfacial tensions critical salt concentration inputs. Multiple coacervates can coexist if they differ sufficiently macromolecular density, associated differences be used predict droplet formation. also distinct chemical environments concentrate guest molecules different extents. Our findings suggest condensate immiscibility may very general feature biological systems, could exploited design self-organized synthetic compartments control biomolecular processes.

Language: Английский

Citations

305
Tunable multiphase dynamics of arginine and lysine liquid condensates DOI Creative Commons
Rachel S. Fisher, Shana Elbaum‐Garfinkle

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Sept. 15, 2020

Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular have potential to drive development novel liquid-based organelles therapeutics, however, an how individual molecules contribute emergent material properties, approaches directly manipulate dynamics are lacking. Here, using microrheology, we demonstrate that droplets poly-arginine coassembled with mono/polynucleotides approximately 100 fold greater viscosity than comparable lysine droplets, both which can be finer tuned by polymer length. We find these amino acid-level differences formation immiscible tunable kinetics further exploited trigger controlled release droplet components. Together, this work provides mechanism leveraging sequence-level components in order regulate multiphase coexistence.

Language: Английский

Citations

247
Coacervates as models of membraneless organelles DOI Creative Commons
N. Amy Yewdall, Alain A.M. André, Tiemei Lu

et al.

Current Opinion in Colloid & Interface Science, Journal Year: 2020, Volume and Issue: 52, P. 101416 - 101416

Published: Dec. 30, 2020

Coacervates are condensed liquid-like droplets, usually formed with oppositely charged polymeric molecules. They have been studied extensively in colloid and interface science for their remarkable material properties. The liquid–liquid phase separation underlying coacervate formation also plays an important role the of various membraneless organelles (MLOs) that found many living cells. Therefore, there is increasing interest to use well-characterized coacervates as vitro models mimic specific aspects MLOs. Here, we review five – physical chemical properties, hierarchical organization, uptake selectivity, dynamics, maturation particular discuss how useful better understand these

Language: Английский

Citations

239
Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies DOI Creative Commons
Taranpreet Kaur, Muralikrishna Raju, Ibraheem Alshareedah

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Feb. 8, 2021

Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network multiple proteins RNAs, their competing molecular play key roles in regulating condensate composition structure. Employing ternary system comprising prion-like polypeptide (PLP), arginine-rich (RRP), RNA, we show that competition between PLP RNA for single shared partner, RRP, leads to RNA-induced demixing PLP-RRP into stable coexisting phases-homotypic heterotypic RRP-RNA condensates. The morphology these biphasic (non-engulfing/ partial engulfing/ complete engulfing) is determined by RNA-to-RRP stoichiometry hierarchy intermolecular interactions, providing glimpse broad range multiphasic patterns accessible Our findings provide minimal set physical rules govern spatial organization multicomponent biomolecular

Language: Английский

Citations

212
Polyelectrolyte Complex Coacervates: Recent Developments and New Frontiers DOI
Artem M. Rumyantsev, Nicholas E. Jackson, Juan Pablo

et al.

Annual Review of Condensed Matter Physics, Journal Year: 2020, Volume and Issue: 12(1), P. 155 - 176

Published: Nov. 24, 2020

Polyelectrolyte complex coacervates represent a wide class of materials with applications ranging from coatings and adhesives to pharmaceutical technologies. They also underpin multiple biological processes, which are only now beginning be deciphered. The means by molecular-scale architecture propagates into macroscopic structure, thermodynamics, dynamics in is central concern physics, chemistry, biology, science. How does polyion charge sequence dictate thermodynamic behavior? one tailor rheology or interfacial tension using macromolecular architecture? What emergent functionality polymer has consequences? Recent developments coacervate science shed light on many these issues raise exciting new challenges for the close integration theory, simulations, experiment.

Language: Английский

Citations

147
The role of liquid–liquid phase separation in regulating enzyme activity DOI
Brian G. O’Flynn, Tanja Mittag

Current Opinion in Cell Biology, Journal Year: 2021, Volume and Issue: 69, P. 70 - 79

Published: Jan. 24, 2021

Language: Английский

Citations

144
Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles DOI
Saehyun Choi, McCauley O. Meyer, Philip C. Bevilacqua

et al.

Nature Chemistry, Journal Year: 2022, Volume and Issue: 14(10), P. 1110 - 1117

Published: June 30, 2022

Language: Английский

Citations

91
Aging can transform single-component protein condensates into multiphase architectures DOI Creative Commons
Adiran Garaizar, Jorge R. Espinosa, Jerelle A. Joseph

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(26)

Published: June 21, 2022

Phase-separated biomolecular condensates that contain multiple coexisting phases are widespread in vitro and cells. Multiphase emerge readily within multicomponent mixtures of biomolecules (e.g., proteins nucleic acids) when the different components present sufficient physicochemical diversity intermolecular forces, structure, chemical composition) to sustain separate phases. Because such is highly coupled solution conditions temperature, pH, salt, composition), it can manifest itself immediately from nucleation growth stages condensate formation, develop spontaneously due external stimuli or progressively as age. Here, we investigate thermodynamic factors explain progressive intrinsic transformation single-component into multiphase architectures during nonequilibrium process aging. We a multiscale model integrates atomistic simulations proteins, sequence-dependent coarse-grained condensates, minimal dynamically aging with nonconservative forces. Our predict initially homogeneous liquid like transform gel-core/liquid-shell liquid-core/gel-shell they age gradual irreversible enhancement interprotein interactions. The type architecture determined by mechanism, molecular organization gel phases, makeup protein. Notably, disorder order transitions prion-like domains intracellular lead required study, therefore, predicts potential mechanism which results condensates.

Language: Английский

Citations

75