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Sequence-dependent biomolecular phase separation driven by short-range interaction: From material properties to
Jun-Qi Li1, Zeng-Shuai Yan2, Yu-Qiang Ma1
1Nanjing University, National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing 210093, China.
Physical Review. E
|June 19, 2025
Summary
Biomolecular condensates form through liquid-liquid phase separation (LLPS). This study reveals how specific molecular sequences dictate condensate properties, offering insights for designing stable, functional biomolecular condensates.
Area of Science:
- Biochemistry
- Biophysics
- Molecular Biology
Background:
- Biomacromolecular liquid-liquid phase separation (LLPS) drives biomolecular condensate formation, essential for cellular functions.
- LLPS is often attributed to nonspecific interactions, but sequence-dependent properties remain underexplored.
Purpose of the Study:
- To investigate how specific molecular sequences influence the material properties of biomolecular condensates.
- To establish a framework for understanding sequence-dependent behavior in LLPS.
Main Methods:
- Theoretical analysis.
- Coarse-grained molecular dynamics simulations.
- Introduction of a sequence descriptor, ϕ*.
Main Results:
- Identified strong correlations between the sequence descriptor ϕ* and material properties (e.g., viscosity, surface tension, diffusion).
- Observed distinct scaling relationships for surface tension and viscosity near critical points, with viscosity being more sensitive.
- Found that high ϕ* sequences can hinder efficient droplet growth.
Conclusions:
- Sequence-specific interactions play a critical role in determining biomolecular condensate properties.
- The findings provide a basis for designing biomolecular condensates with tunable stability and dynamics.
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