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Diffusion of intrinsically disordered proteins within protein condensates

Fuga Watanabe1, Takuma Akimoto2, Robert B. Best3, Kresten Lindorff-Larsen4, Ralf Metzler5,6, and Eiji Yamamoto1,*

  • *Contact author: eiji.yamamoto@sd.keio.ac.jp
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Phys. Rev. Research 7, 043117 – Published 30 October, 2025

DOI: https://doi.org/10.1103/jsdl-chm9

Abstract

Many intrinsically disordered proteins (IDPs) may undergo a phase separation to form a biomolecular condensate. Understanding the behavior of individual molecules within condensates is crucial for characterizing their collective physical properties relevant to biological functions. Here, we investigate the diffusion dynamics of IDPs within protein condensates using molecular dynamics simulations. We find that the proteins exhibit transient subdiffusion due to the viscoelastic nature of the condensates. Under conditions when confinement arises from the finite size of the droplet, the conformation and instantaneous diffusivity of the proteins vary significantly between the droplet interior and the interface with the environment, resulting in non-Gaussian displacement distributions. Moreover, we demonstrate that the structural complexity and intermolecular interactions of proteins modulate the subdiffusive behavior and the relaxation of diffusivity fluctuations. This study highlights key aspects of the heterogeneous structural and dynamical behavior of IDPs within biomolecular condensates.

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Phys. Rev. Research 7, 043117– Published 30 October, 2025
  • Received 14 January 2024
  • Accepted 23 September 2025
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