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Related Experiment Video

Updated: Jan 17, 2026

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Multiphase separation in postsynaptic density regulated by membrane geometry via interaction valency and volume.

Risa Yamada1, Giovanni B Brandani1, Shoji Takada1

  • 1Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan.

Elife
|September 23, 2025
PubMed
Summary

Biomolecular condensates exhibit distinct phase behaviors in solution versus on membranes. This study reveals how CaMKII

Keywords:
biomolecular condensateliquid-liquid phase separationmolecular biophysicsmulti-phase condensatenonepostsynaptic densitystructural biology

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Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Biology

Background:

  • Biomolecular condensates are dynamic cellular structures involved in various biological processes.
  • These condensates can exhibit complex multiphase morphologies, such as core-shell structures, influencing their function.
  • The postsynaptic density, containing AMPA receptor, NMDA receptor, PSD-95, and CaMKII, shows a puzzling reversed multiphase morphology between solution and membrane states.

Purpose of the Study:

  • To investigate the multiphase behavior of biomolecular condensates in solution (3D) and on membranes (2D).
  • To elucidate the molecular mechanisms driving the reversed morphology of postsynaptic density components.
  • To understand the differences between condensate formation in solution and membrane domain formation.

Main Methods:

  • Computational simulations were employed to model condensate behavior.
  • The study focused on the interactions between AMPA receptor, NMDA receptor, PSD-95, and CaMKII.
  • Simulations analyzed condensate morphology in both 3D solution and 2D membrane environments.

Main Results:

  • Simulations reproduced a core-shell structure in 3D solution (AMPA-receptor/PSD-95 core, NMDA-receptor/CaMKII shell) upon CaMKII activation.
  • A reversed morphology was observed on the membrane, driven by CaMKII's high valency and large volume.
  • In solution, CaMKII's non-specific volume interaction dominates; on the membrane, specific multivalent interactions prevail over excluded volume effects.

Conclusions:

  • The study highlights distinct mechanisms governing condensate formation in solution versus membrane domain formation.
  • CaMKII's valency and excluded volume significantly influence condensate morphology and phase separation.
  • Layered arrangements of receptors and CaMKII modulate interactions, favoring multivalent binding on membranes.