Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics

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.