Distribution of polyelectrolytes and counterions upon polyelectrolyte complexation DOI Creative Commons
Giulia Allegri, Jurriaan Huskens, Ricardo P. Martinho

et al.

Journal of Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 672, P. 654 - 663

Published: June 7, 2024

Understanding polyelectrolyte complexation remains limited due to the absence of a systematic methodology for analyzing distribution components between complex (PEC) and dilute phases. We developed based on NMR quantify all solid-like PECs their supernatant phases formed by mixing different ratios poly(allylamine hydrochloride) (PAH) poly(acrylic acid)-sodium salt (PAA). This approach allowed determining relative absolute concentrations polyelectrolytes in both 1H studies. Using 23Na 35Cl spectroscopy we measured concentration counterions Regardless ratio PEC is charge-stoichiometric, any excess achieve charge stoichiometry phase. The majority were found phase, confirming counterion release being major thermodynamic driving force formation. phase approximately twice as high complete mass balance formation could be determined translated into molecular picture. It appears that PAH fully charged, while PAA more protonated, so less some 10% extrinsic PAH-Cl- pairs are present complex.

Language: Английский

Thermodynamic forces from protein and water govern condensate formation of an intrinsically disordered protein domain DOI Creative Commons
Saumyak Mukherjee, Lars V. Schäfer

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 21, 2023

Liquid-liquid phase separation (LLPS) can drive a multitude of cellular processes by compartmentalizing biological cells via the formation dense liquid biomolecular condensates, which function as membraneless organelles. Despite its importance, molecular-level understanding underlying thermodynamics this process remains incomplete. In study, we use atomistic molecular dynamics simulations low complexity domain (LCD) human fused in sarcoma (FUS) protein to investigate contributions water and molecules free energy changes that govern LLPS. Both components are found have comparably sizeable thermodynamic FUS condensates. Moreover, quantify counteracting effects released into bulk upon condensate waters retained within droplets. Among various factors considered, solvation entropy interaction enthalpy identified most important contributions, while smaller. These results provide detailed insights on intricate interplay between protein- solvation-related forces

Language: Английский

Citations

49
The role of biomolecular condensates in protein aggregation DOI
Brent S. Visser, Wojciech P. Lipiński, Evan Spruijt

et al.

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(9), P. 686 - 700

Published: Aug. 12, 2024

Language: Английский

Citations

23
Expanding the molecular grammar of polar residues and arginine in FUS phase separation DOI
Noah Wake, Shuo-Lin Weng, Tongyin Zheng

et al.

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

Citations

3
Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates DOI

Guangle Li,

Chengqian Yuan, Xuehai Yan

et al.

Soft Matter, Journal Year: 2025, Volume and Issue: 21(10), P. 1781 - 1812

Published: Jan. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Language: Английский

Citations

2
Entropy Tug-of-War Determines Solvent Effects in the Liquid–Liquid Phase Separation of a Globular Protein DOI Creative Commons
Saumyak Mukherjee, Sashary Ramos, Simone Pezzotti

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(15), P. 4047 - 4055

Published: April 5, 2024

Liquid–liquid phase separation (LLPS) plays a key role in the compartmentalization of cells via formation biomolecular condensates. Here, we combined atomistic molecular dynamics (MD) simulations and terahertz (THz) spectroscopy to determine solvent entropy contribution condensates human eye lens protein γD-Crystallin. The MD reveal an tug-of-war between water molecules that are released from droplets those retained within condensates, two categories were also assigned spectroscopically. A recently developed THz-calorimetry method enables quantitative comparison experimental computational changes molecules. strong correlation mutually validates approaches opens way detailed atomic-level understanding different driving forces underlying LLPS.

Language: Английский

Citations

12
Label-Free Techniques for Probing Biomolecular Condensates DOI
Khalid A. Ibrahim,

Akhil S. Naidu,

Helena Miljkovic

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(16), P. 10738 - 10757

Published: April 12, 2024

Biomolecular condensates play important roles in a wide array of fundamental biological processes, such as cellular compartmentalization, regulation, and other biochemical reactions. Since their discovery first observations, an extensive expansive library tools has been developed to investigate various aspects properties, encompassing structural compositional information, material evolution throughout the life cycle from formation eventual dissolution. This Review presents overview expanded set methods that researchers use probe properties biomolecular across diverse scales length, concentration, stiffness, time. In particular, we review recent years' exciting development label-free techniques methodologies. We broadly organize into 3 categories: (1) imaging-based techniques, transmitted-light microscopy (TLM) Brillouin (BM), (2) force spectroscopy atomic (AFM) optical tweezer (OT), (3) microfluidic platforms emerging technologies. point out tools' key opportunities, challenges, future perspectives analyze correlative potential well compatibility with techniques. Additionally, namely, differential dynamic (DDM) interferometric scattering (iSCAT), have huge for applications studying condensates. Finally, highlight how some these can be translated diagnostics therapy purposes. hope this serves useful guide new field aids advancing biophysical study

Language: Английский

Citations

11
Unlocking the electrochemical functions of biomolecular condensates DOI
Yifan Dai, Zhen‐Gang Wang, Richard N. Zare

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(11), P. 1420 - 1433

Published: Sept. 26, 2024

Language: Английский

Citations

10
pH-Responsive Phase Separation Dynamics of Intrinsically Disordered Peptides DOI Creative Commons
Manali Nandy, Ketan A. Ganar, Hans Ippel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract Liquid-liquid phase separation of biomolecules is crucial for maintaining the functional organization in biological systems. Intrinsically disordered proteins are particularly prone to form phase-separated condensates response various physicochemical triggers. While effect ionic strength and temperature on dynamics have been studied extensively, influence pH less explored. Here, we study a model glycine-rich protein present tick bioadhesive, given its capability undergo separation. After confirming nature through spectroscopy, investigated dependence underlying molecular mechanisms. Our findings reveal that significantly influences hydrophobicity via residues, driving notable variations coacervation behavior (propensity, progression) shaping material properties (viscosity, interfacial activity) formed condensates. Given ubiquitous presence biology, this provides valuable insights about broad implications pH-dependent intrinsically proteins.

Language: Английский

Citations

1
Solution NMR goes big: Atomic resolution studies of protein components of molecular machines and phase-separated condensates DOI
Alexander I. M. Sever, Rashik Ahmed, Philip Rößler

et al.

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 90, P. 102976 - 102976

Published: Jan. 20, 2025

Language: Английский

Citations

1
Toward Accurate Simulation of Coupling between Protein Secondary Structure and Phase Separation DOI
Yumeng Zhang, Shanlong Li, Xiping Gong

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 342 - 357

Published: Dec. 19, 2023

Intrinsically disordered proteins (IDPs) frequently mediate phase separation that underlies the formation of a biomolecular condensate. Together with theory and experiment, efficient coarse-grained (CG) simulations have been instrumental in understanding sequence-specific IDPs. However, widely used Cα-only models are limited capturing peptide nature IDPs, particularly backbone-mediated interactions effects secondary structures, separation. Here, we describe hybrid resolution (HyRes) protein model toward more accurate description backbone transient structures With an atomistic side chains, HyRes can semiquantitatively capture residue helical propensity overall chain dimension monomeric Using GY-23 as system, show is enough for direct simulation spontaneous and, at same time, appears to resolve single His Lys mutations. also successfully predict increased β-structure condensate, consistent available experimental CD data. We further utilize study TPD-43, where several disease-related mutants conserved region (CR) shown affect residual helicities modulate measured by saturation concentration. The recapitulate effect these on helicity TDP-43 CR. Analyses reveal balance between chain-mediated interactions, but not itself, actually determines propensity. These results support represents effective molecular IDP will help elucidate coupling

Language: Английский

Citations

21