Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics
Year: 2026
Type: article
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.
Source: PRX Life
DOI: 10.1103/h9cl-j5x5
Institution: Johns Hopkins University
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: National Science Foundation, U.S. Department of Energy, Alfred P. Sloan Foundation, Gordon and Betty Moore Foundation, Johns Hopkins University, National Institutes of Health, Office of Naval Research, National Institute of General Medical Sciences, Kavli Institute for Theoretical Physics, University of California, Santa Barbara
Awards: G1813104318, G3398237449, G3535732435, G3792763473, G4059986048, G4238527680, G4689434848, G5356677024, Collaborative Research: SHF Medium: A language for molecular communication using temporal codes, G6636132319, Kavli Institute for Theoretical Physics, PROGRAMMABLE DYNAMIC SELF-ASSEMBLY OF DNA NANOSTRUCTURES, The Chemistry-Biology Interface Program at Johns Hopkins University, G876022237, The Chemistry-Biology Interface Program at Johns Hopkins University
OpenAlex ID: W7164138053