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Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
Published on: January 5, 2024
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Controlling interfacial protein adsorption, desorption and aggregation in biomolecular condensates
Brent S Visser1, Merlijn H I van Haren1, Wojciech P Lipiński1,2
1Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
Nature Communications
|November 19, 2025
Summary
Alpha-synuclein (αSyn) protein aggregation at condensate interfaces accelerates age-related diseases. Modulating this adsorption, through strategies like altering surface charge or competitive binding, can slow harmful protein aggregation.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Protein aggregation, particularly of amyloidogenic proteins like alpha-synuclein (αSyn), is implicated in various age-related neurodegenerative diseases.
- Biomolecular condensates and their interfaces can influence protein aggregation kinetics, often promoting faster aggregation.
- Understanding the mechanisms of αSyn localization at condensate interfaces is critical for therapeutic interventions.
Purpose of the Study:
- To elucidate the mechanism of αSyn adsorption to peptide-based heterotypic condensate interfaces.
- To identify factors governing αSyn localization, including condensate properties and protein characteristics.
- To design and test strategies for modulating αSyn accumulation at condensate interfaces.
Main Methods:
- Investigated αSyn adsorption to peptide-based heterotypic condensates.
- Analyzed the influence of condensate surface charge and protein amphiphilicity on adsorption.
- Quantified adsorption reversibility and concentration dependence.
- Designed and implemented strategies involving biomolecule addition, competitive protein adsorption, and membrane preferential binding.
Main Results:
- αSyn localization to condensate surfaces is a reversible, multi-layered adsorption process.
- Adsorption is governed by condensate surface charge and αSyn's amphiphilic nature, plateauing at micromolar concentrations.
- Strategies including decreasing condensate ζ-potential (e.g., with NTPs, RNA), competitive adsorption (e.g., G3BP1, Hsp70), and membrane preferential binding effectively modulated αSyn accumulation.
- Removing αSyn from condensate interfaces significantly reduced aggregation rates.
Conclusions:
- αSyn adsorption to condensate interfaces is a key driver of accelerated aggregation in age-related diseases.
- Modulating condensate surface properties and employing competitive binding agents are viable strategies to control αSyn accumulation.
- These findings offer potential therapeutic avenues for neurodegenerative diseases by targeting protein-condensate interactions.
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