Dehydration entropy drives liquid-liquid phase separation by molecular crowding.

Area of Science:

• Biophysics
• Polymer Science
• Cell Biology

Background:

• Liquid-liquid phase separation (LLPS) is a key cellular process involving biopolymers.
• Protein complexity often obscures fundamental drivers of LLPS.
• Understanding LLPS drivers is crucial for cell biology and biomaterials.

Purpose of the Study:

• To investigate the role of polyethylene glycol (PEG) in driving LLPS.
• To determine if LLPS can occur without protein-specific properties like hydrophobicity.
• To elucidate the mechanism by which PEG influences LLPS.

Main Methods:

• Utilized charged polymers lacking hydrophobicity and sequence complexity.
• Employed experimental techniques and field-theoretic simulations.
• Analyzed PEG's partitioning behavior in the coacervate phase.

Main Results:

• Successfully recapitulated entropy-driven LLPS with simple charged polymers.
• Demonstrated significant enhancement of LLPS propensity by PEG.
• Confirmed PEG drives LLPS via polymer dehydration without partitioning into the coacervate phase.

Conclusions:

• LLPS can be driven by simple polymer dehydration, independent of protein complexity.
• PEG acts as a crucial molecular crowder, modulating LLPS through excluded volume effects.
• This work provides fundamental insights into LLPS, applicable to both biological systems and synthetic materials.