Dynamics of protein condensates in weak-binding regime

Area of Science:

• Biophysics
• Soft Matter Physics
• Molecular Biology

Background:

• Intracellular liquid-liquid phase separation is driven by weak interactions between proteins and nucleic acids.
• The sticker-spacer model explains the phase behavior of multivalent molecules.
• The role of specific sticker interactions in condensate rheology is not fully understood, especially in the weak-binding regime.

Purpose of the Study:

• To investigate the controlling factors of structure and dynamics in weak-binding condensates.
• To understand how binding energy influences condensate properties like diffusivity and viscosity.
• To differentiate the mechanisms governing dynamics in weak-binding versus strong-binding regimes.

Main Methods:

• Development of a mean-field theory based on associative polymer thermodynamics.
• Molecular-dynamics simulations utilizing the sticker-spacer model.
• Scaling analysis to determine relationships between binding energy, free sticker fraction, and diffusivity.

Main Results:

• In the weak-binding regime, condensate dynamics are governed by the free sticker fraction (Wf), not bond lifetime.
• Diffusivity (D) and free sticker fraction (Wf) decrease with increasing binding energy (ɛb), following D∝Wf∝e^{-0.5ɛb}.
• Zero-shear viscosity (η) scales with binding energy as η∝e^{0.5ɛb}, indicating a free-sticker-dominated diffusivity mechanism.

Conclusions:

• The internal dynamics and rheological properties of weak-binding condensates are primarily controlled by the availability of free stickers.
• Binding energy is a key parameter that can be tuned to modulate condensate structure, diffusivity, and viscosity.
• These findings offer a testable framework for experimentally controlling condensate properties through specific binding interactions.