Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.
5 affiliations
- 1Department of Physics & Astronomy, Johns Hopkins University, Baltimore, Maryland 21218, USA.
- 2Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, USA.
- 3Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
- 4Department of Computer Science, Johns Hopkins University, Baltimore, Maryland 21218, USA.
- 5Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Abstract
An increasing number of biomolecules have been shown to phase-separate into biomolecular condensates-membraneless subcellular compartments capable of regulating distinct biochemical processes within living cells. The speed with which they exchange components with the cellular environment can influence how fast biochemical reactions occur inside condensates and how fast condensates respond to environmental changes, thereby directly impacting condensate function. While fluorescence recovery after photobleaching (FRAP) experiments are routinely performed to measure this exchange timescale, it remains a challenge to distinguish the various physical processes limiting fluorescence recovery and identify each associated timescale. Here, we present a reaction-diffusion model for condensate exchange dynamics and show that such exchange can differ significantly from that of conventional liquid droplets due to the presence of a percolated molecular network, which gives rise to different mobility species in the dense phase. In this model, exchange can be limited by diffusion of either the high- or low-mobility species in the dense phase, diffusion in the dilute phase, or the attachment (detachment) of molecules to (from) the network at the surface or throughout the bulk of the condensate. Combining analytic derivations and numerical simulations, we quantify the contributions of these distinct physical processes to the overall exchange timescale and predict an experimentally testable scaling relationship between the exchange timescale and condensate size. Our theory suggests that the exchange dynamics can be accelerated via a pore-mediated pathway in which molecules pass through the pores of the meshwork and attach directly in the condensate interior. Notably, this pathway permits a parameter regime in which the exchange timescale becomes independent of condensate size, a scaling behavior that is supported by our FRAP measurements on a biosynthetic DNA nanostar system. Our work offers insight into the rate-limiting physical processes that can control condensate material exchange, with implications for natural and engineered systems.
Related
- Scaffold Affinity Tunes Biomolecular Condensate Function
- Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation
- Spatial metabolomics-guided deep learning framework for dissecting immune evasion mechanisms in fungal infection microenvironments
- A Molecular Rotor-Based Platform for Dissecting Protein Phase Separation and Aggregation
- Dissecting the molecular basis of reduced stability in staphylokinase variant 42D
BibTeX
@article{kliegman2026dissecting,
title = {{Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.}},
author = {Ross Kliegman and Eli Kengmana and Rebecca Schulman and Yaojun Zhang},
journal = {PRX life},
year = {2026},
month = jul,
doi = {10.1103/h9cl-j5x5},
url = {https://europepmc.org/article/MED/42847104},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.
AU - Ross Kliegman
AU - Eli Kengmana
AU - Rebecca Schulman
AU - Yaojun Zhang
PY - 2026
DA - 2026/07/20
JO - PRX life
DO - 10.1103/h9cl-j5x5
UR - https://europepmc.org/article/MED/42847104
AB - An increasing number of biomolecules have been shown to phase-separate into biomolecular condensates-membraneless subcellular compartments capable of regulating distinct biochemical processes within living cells. The speed with which they exchange components with the cellular environment can influence how fast biochemical reactions occur inside condensates and how fast condensates respond to environmental changes, thereby directly impacting condensate function. While fluorescence recovery after photobleaching (FRAP) experiments are routinely performed to measure this exchange timescale, it remains a challenge to distinguish the various physical processes limiting fluorescence recovery and identify each associated timescale. Here, we present a reaction-diffusion model for condensate exchange dynamics and show that such exchange can differ significantly from that of conventional liquid droplets due to the presence of a percolated molecular network, which gives rise to different mobility species in the dense phase. In this model, exchange can be limited by diffusion of either the high- or low-mobility species in the dense phase, diffusion in the dilute phase, or the attachment (detachment) of molecules to (from) the network at the surface or throughout the bulk of the condensate. Combining analytic derivations and numerical simulations, we quantify the contributions of these distinct physical processes to the overall exchange timescale and predict an experimentally testable scaling relationship between the exchange timescale and condensate size. Our theory suggests that the exchange dynamics can be accelerated via a pore-mediated pathway in which molecules pass through the pores of the meshwork and attach directly in the condensate interior. Notably, this pathway permits a parameter regime in which the exchange timescale becomes independent of condensate size, a scaling behavior that is supported by our FRAP measurements on a biosynthetic DNA nanostar system. Our work offers insight into the rate-limiting physical processes that can control condensate material exchange, with implications for natural and engineered systems.
SN - 2835-8279
ER -