Coacervate Droplets for Synthetic Cells DOI Creative Commons

Zi Lin,

Thomas Beneyton, Jean‐Christophe Baret

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: July 18, 2023

Abstract The design and construction of synthetic cells – human‐made microcompartments that mimic features living have experienced a real boom in the past decade. While many efforts been geared toward assembling membrane‐bounded compartments, coacervate droplets produced by liquid–liquid phase separation emerged as an alternative membrane‐free compartmentalization paradigm. Here, dual role cell research is discussed: encapsulated within membrane‐enclosed coacervates act surrogates membraneless organelles ubiquitously found cells; alternatively, they can be viewed crowded cytosol‐like chassis for constructing integrated cells. After introducing key concepts coacervation illustrating chemical diversity systems, their physicochemical properties resulting bioinspired functions are emphasized. Moving from suspensions free floating coacervates, two nascent roles these highlighted: organelle‐like modules templates. Building discussion on recent studies literature, potential to assemble capable multiple life‐inspired showcased. Future challenges still tackled field finally discussed.

Language: Английский

Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains DOI
Anne Bremer, Mina Farag, Wade M. Borcherds

et al.

Nature Chemistry, Journal Year: 2021, Volume and Issue: 14(2), P. 196 - 207

Published: Dec. 20, 2021

Language: Английский

Citations

398
Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions DOI Creative Commons
Georg Krainer, Timothy J. Welsh, Jerelle A. Joseph

et al.

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

Published: Feb. 17, 2021

Abstract Liquid–liquid phase separation of proteins underpins the formation membraneless compartments in living cells. Elucidating molecular driving forces underlying protein transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, Annexin A11, can reenter phase-separated regime high concentrations. By bringing together experiments simulations, demonstrate this reentrant transition high-salt driven by hydrophobic non-ionic interactions, mechanistically distinct from low-salt regime, where are additionally stabilized electrostatic forces. Our work thus sheds light on cooperation interactions as general condensation process, with important implications aberrant function, druggability, material properties biomolecular condensates.

Language: Английский

Citations

389
Accurate model of liquid–liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties DOI
Giulio Tesei, Thea K. Schulze, Ramón Crehuet

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(44)

Published: Oct. 29, 2021

Significance Cells may compartmentalize proteins via a demixing process known as liquid–liquid phase separation (LLPS), which is often driven by intrinsically disordered (IDPs) and regions. Protein condensates arising from LLPS develop into insoluble protein aggregates, in neurodegenerative diseases cancer. Understanding the of formation, dissolution, aging requires models that accurately capture underpinning interactions at residue level. In this work, we leverage data biophysical experiments on IDPs dilute solution to sequence-dependent model predicts conformational behavior diverse unrelated sequences with good accuracy. Using model, gain insight coupling between chain compaction propensity.

Language: Английский

Citations

287
Peptide-Based Supramolecular Systems Chemistry DOI

Fahmeed K. Sheehan,

Deborah Sementa, Ankit Jain

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(22), P. 13869 - 13914

Published: Sept. 14, 2021

Peptide-based supramolecular systems chemistry seeks to mimic the ability of life forms use conserved sets building blocks and chemical reactions achieve a bewildering array functions. Building on design principles for short peptide-based nanomaterials with properties, such as self-assembly, recognition, catalysis, actuation, are increasingly available. is starting address far greater challenge systems-level access complex functions that emerge when multiple interactions coordinated integrated. We discuss key features relevant design, including regulating order disorder, development active adaptive by considering kinetic thermodynamic aspects combinatorial dynamic covalent noncovalent interactions. Finally, we how structural concepts, preorganization induced fit, critical develop materials tunable photonic, electronic, catalytic properties. highlight examples where combined, resulting in display properties cannot be achieved without this level integration.

Language: Английский

Citations

281
Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy DOI
Jerelle A. Joseph,

Aleks Reinhardt,

Anne Aguirre

et al.

Nature Computational Science, Journal Year: 2021, Volume and Issue: 1(11), P. 732 - 743

Published: Nov. 22, 2021

Language: Английский

Citations

257
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
The molecular basis for cellular function of intrinsically disordered protein regions DOI
Alex S. Holehouse, Birthe B. Kragelund

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 187 - 211

Published: Nov. 13, 2023

Language: Английский

Citations

235
Intrinsically disordered protein regions and phase separation: sequence determinants of assembly or lack thereof DOI
Erik Martin, Alex S. Holehouse

Emerging Topics in Life Sciences, Journal Year: 2020, Volume and Issue: 4(3), P. 307 - 329

Published: Oct. 20, 2020

Intrinsically disordered protein regions (IDRs) — that do not fold into a fixed three-dimensional structure but instead exist in heterogeneous ensemble of conformations have recently entered mainstream cell biology the context liquid–liquid phase separation (LLPS). IDRs are frequently found to be enriched phase-separated compartments. Due this observation, presence an IDR is assumed diagnostic its ability separate. In review, we clarify role biological assembly and explore physical principles through which amino acids can confer attractive molecular interactions underlie separation. While some will robustly drive separation, many others not. We emphasize rather than ‘disorder' driving multivalency drives As such, whether or region capable depend on chemistry encoded within acid sequence. Consequently, in-depth understanding prerequisite make informed inferences how why may involved or, more generally, protein-mediated intermolecular interactions.

Language: Английский

Citations

225
Extreme dynamics in a biomolecular condensate DOI
Nicola Galvanetto, Miloš T. Ivanović, Aritra Chowdhury

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7971), P. 876 - 883

Published: July 19, 2023

Language: Английский

Citations

189
Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides DOI Creative Commons
Ibraheem Alshareedah, Mahdi Muhammad Moosa, Matthew Pham

et al.

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

Published: Nov. 16, 2021

Abstract Liquid-liquid phase separation of multivalent proteins and RNAs drives the formation biomolecular condensates that facilitate membrane-free compartmentalization subcellular processes. With recent advances, it is becoming increasingly clear are network fluids with time-dependent material properties. Here, employing microrheology optical tweezers, we reveal molecular determinants govern viscoelastic behavior formed by Arg/Gly-rich sticker-spacer polypeptides RNA. These behave as Maxwell an elastically-dominant rheological response at shorter timescales a liquid-like longer timescales. The viscous elastic regimes these can be tuned polypeptide RNA sequences well their mixture compositions. Our results establish quantitative link between sequence- structure-encoded interactions microscopic scale properties resulting mesoscale, enabling route to systematically probe rationally engineer programmable mechanics.

Language: Английский

Citations

181