Phase separation vs aggregation behavior for model disordered proteins

Area of Science:

• Biophysics
• Computational Biology
• Cell Biology

Background:

• Liquid-liquid phase separation (LLPS) is crucial for cellular organization and biochemical regulation.
• Protein LLPS is sequence-dependent, but sequence features dictating phase transition and morphology remain unclear.

Purpose of the Study:

• To investigate how sequence distribution, sticker fraction, and chain length influence protein phase separation versus finite aggregation.
• To identify sequence properties that predict the type of phase transition in disordered proteins.

Main Methods:

• Employed grand canonical Monte Carlo simulations.
• Utilized a coarse-grained model for disordered proteins.
• Systematically varied sequence distribution, sticker fraction, and chain length.

Main Results:

• Introduced a normalized sequence charge decoration (SCD) parameter as a predictive criterion for macroscopic phase separation versus finite aggregation.
• Demonstrated a strong correlation between the SCD parameter and the critical density for phase separation.
• Found that longer chain lengths generally favor macroscopic phase separation for most sequences.

Conclusions:

• The SCD parameter provides a quantitative link between protein sequence properties and phase behavior.
• Macroscopic LLPS is likely the dominant phase transition for disordered proteins with dominant short-ranged attractive interactions.
• Findings offer insights into the widespread observation of LLPS in cellular environments.