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Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.

Ross Kliegman1, Eli Kengmana2, Rebecca Schulman2,3,4

  • 1Department of Physics & Astronomy, Johns Hopkins University, Baltimore, Maryland 21218, USA.

Biorxiv : the Preprint Server for Biology
|June 6, 2025
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Summary
This summary is machine-generated.

Biomolecular condensates regulate cell processes, but their exchange dynamics are complex. This study introduces a model revealing how molecular networks and diffusion rates impact condensate function and size-dependent exchange timescales.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biochemistry

Background:

  • Biomolecular condensates are membraneless compartments regulating cellular processes.
  • Condensate component exchange influences reaction rates and cellular responses.
  • Fluorescence Recovery After Photobleaching (FRAP) measures exchange but struggles to resolve underlying physical processes.

Purpose of the Study:

  • To develop a reaction-diffusion model for biomolecular condensate exchange dynamics.
  • To differentiate physical processes limiting fluorescence recovery within condensates.
  • To quantify contributions of distinct physical mechanisms to condensate exchange timescales.

Main Methods:

  • Developed a reaction-diffusion model incorporating percolated molecular networks.
  • Performed analytic derivations and numerical simulations for various exchange limitation scenarios.
  • Utilized a biosynthetic DNA nanostar system for experimental validation.

Main Results:

  • Condensate exchange differs from liquid droplets due to molecular networks and varied mobility species.
  • Exchange can be limited by diffusion (dense/dilute phases) or molecular attachment/detachment.
  • A novel regime of non-quadratic scaling between exchange timescale and condensate size was observed.

Conclusions:

  • The model elucidates predominant physical mechanisms governing condensate material exchange.
  • Provides an experimentally testable relationship between exchange timescale and condensate size.
  • Highlights a new scaling regime with implications for condensate dynamics and function.