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Liquid-liquid phase separation driven by charge heterogeneity.

Daniele Notarmuzi1, Emanuela Bianchi1,2

  • 1Institut für Theoretische Physik, TU Wien, Wiedner Hauptstraße 8-10, A-1040 Wien, Austria.

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|January 13, 2025
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Summary
This summary is machine-generated.

Protein charge heterogeneity influences liquid-liquid phase separation (LLPS). This study reveals how charge anisotropy, both attractive and repulsive, significantly lowers critical parameters for LLPS, impacting protein condensation.

Keywords:
Biological physicsPhase transitions and critical phenomena

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Area of Science:

  • Biophysics
  • Soft Matter Physics
  • Computational Biology

Background:

  • Protein charge heterogeneity is key to liquid-liquid phase separation (LLPS).
  • Understanding electrostatic anisotropy's role in protein LLPS is limited.
  • LLPS is crucial for cellular organization and function.

Purpose of the Study:

  • To investigate the impact of protein surface charge patchiness and net charge on LLPS.
  • To develop a model that quantifies the effects of electrostatic anisotropy on LLPS critical points.
  • To elucidate the mechanisms by which charge anisotropy influences protein condensation.

Main Methods:

  • Utilized a coarse-grained model with a mean-field description.
  • Extended the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for non-uniformly charged particles.
  • Numerically simulated systems with varying surface charge patchiness and net charge.

Main Results:

  • Charge anisotropy, particularly directional repulsion, significantly reduces LLPS critical parameters (temperature and density).
  • A thermodynamic-independent parameter, based on orientationally averaged pair properties, effectively estimates particle connectivity and condensation propensity.
  • Directional attraction lowers bonding valence, while directional repulsion imposes morphological constraints, hindering dense aggregate formation.

Conclusions:

  • Protein charge anisotropy is a critical determinant of LLPS behavior.
  • The developed model provides a quantitative framework for understanding electrostatics in protein phase separation.
  • Charge anisotropy, especially repulsion, plays a significant role in regulating the formation and stability of protein condensates.