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Updated: Jun 20, 2026
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Microfluidic Mixers for Studying Protein Folding
Published on: April 10, 2012
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Taylor Dispersion-Induced Phase Separation for the Efficient Characterisation of Protein Condensate Formation
Rasmus K Norrild1, Thomas O Mason1, Lars Boyens-Thiele1
1Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 227, 2800, Kgs. Lyngby, Denmark.
Angewandte Chemie (International Ed. in English)
|April 9, 2024
Summary
We developed Taylor dispersion-induced phase separation (TDIPS), a microfluidic method to study protein liquid-liquid phase separation (LLPS) in vitro. TDIPS efficiently screens LLPS behavior and drug interactions using minimal sample volumes.
Area of Science:
- Biochemistry
- Cell Biology
- Biophysics
Background:
- Biomolecular condensates are crucial for cellular functions and implicated in diseases.
- Liquid-liquid phase separation (LLPS) is the proposed mechanism for condensate formation.
- Understanding protein LLPS in vitro is essential for drug development.
Purpose of the Study:
- To introduce Taylor dispersion-induced phase separation (TDIPS) as a novel method for studying protein LLPS.
- To demonstrate the efficiency and versatility of TDIPS in characterizing phase separation phenomena.
- To explore the potential of TDIPS in drug screening for modulating LLPS.
Main Methods:
- Development and application of a microfluidic platform for TDIPS.
- Utilizing nanoliter sample volumes without fluorescent labels.
- Screening phase behavior of proteins PGL-3 and Ddx4, and probing reversibility of α-synuclein and lysozyme assemblies.
Main Results:
- TDIPS robustly measures condensation phenomena with minimal sample and no labels.
- Unexpected re-entrant LLPS behavior observed for PGL-3 and Ddx4 at low ionic strength.
- Demonstrated reversibility of protein assemblies and efficient screening of LLPS-modifying compounds.
Conclusions:
- TDIPS is a powerful, efficient, and accessible tool for in vitro studies of protein LLPS.
- The method reveals novel insights into protein phase separation behavior, including re-entrant phenomena.
- TDIPS facilitates high-throughput screening for compounds that modulate biomolecular condensate formation.
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