Enzymatically Driven Remodeling of Growth Kinetics and Internal Structure in Biomolecular Condensates
Abstract
Living cells exhibit a complex organization comprising numerous compartments, among which are RNA- and protein-rich membraneless, liquidlike organelles known as biomolecular condensates. Energy-consuming processes regulate their formation and dissolution, with (de)phosphorylation by specific enzymes being among the most commonly involved reactions. By employing a model system consisting of a phosphorylatable peptide and homopolymeric RNA, and thanks to time-resolved ultra-small-angle x-ray scattering enabling us to probe a wide range of length and time scales, we elucidate how enzymatic activity remodels the growth kinetics and the internal structure of biomolecular condensates. Under a passive condition, we reveal a nucleation-driven coalescence mechanism maintained over four decades in time, similar to the coarsening of simple binary fluid mixtures. Coarse-grained molecular-dynamics simulations show that peptide-decorated RNA chains assembled immediately after mixing constitute the basic subunits. In contrast, actively formed condensates initially display a networklike internal structure, which gradually matures upon dephosphorylation prior to coalescence. Both pathways lead to a steady state, but fluorescence recovery after photobleaching indicates a peptide diffusivity that is twice as high in actively formed condensates consistent with their loosely packed internal structure. This study contributes to linking effectively cellular active processes such as post-translational modifications to the formation and dissolution pathways of membraneless organelles, impacting other fields including synthetic biology.
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BibTeX
@article{sundararajan2026enzymatically,
title = {{Enzymatically Driven Remodeling of Growth Kinetics and Internal Structure in Biomolecular Condensates}},
author = {Tamizhmalar Sundararajan and Matteo Boccalini and Roméo Suss and Sandrine Mariot and Emerson R da Silva and Fernando C Giacomelli and Austin Hubley and Theyencheri Narayanan and Alessandro Barducci and Guillaume Tresset},
journal = {PRX Life},
year = {2026},
month = oct,
doi = {10.1103/n8nd-sgs6},
url = {https://hal.science/hal-05796880v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Enzymatically Driven Remodeling of Growth Kinetics and Internal Structure in Biomolecular Condensates
AU - Tamizhmalar Sundararajan
AU - Matteo Boccalini
AU - Roméo Suss
AU - Sandrine Mariot
AU - Emerson R da Silva
AU - Fernando C Giacomelli
AU - Austin Hubley
AU - Theyencheri Narayanan
AU - Alessandro Barducci
AU - Guillaume Tresset
PY - 2026
DA - 2026/10/08
JO - PRX Life
DO - 10.1103/n8nd-sgs6
UR - https://hal.science/hal-05796880v1
AB - Living cells exhibit a complex organization comprising numerous compartments, among which are RNA- and protein-rich membraneless, liquidlike organelles known as biomolecular condensates. Energy-consuming processes regulate their formation and dissolution, with (de)phosphorylation by specific enzymes being among the most commonly involved reactions. By employing a model system consisting of a phosphorylatable peptide and homopolymeric RNA, and thanks to time-resolved ultra-small-angle x-ray scattering enabling us to probe a wide range of length and time scales, we elucidate how enzymatic activity remodels the growth kinetics and the internal structure of biomolecular condensates. Under a passive condition, we reveal a nucleation-driven coalescence mechanism maintained over four decades in time, similar to the coarsening of simple binary fluid mixtures. Coarse-grained molecular-dynamics simulations show that peptide-decorated RNA chains assembled immediately after mixing constitute the basic subunits. In contrast, actively formed condensates initially display a networklike internal structure, which gradually matures upon dephosphorylation prior to coalescence. Both pathways lead to a steady state, but fluorescence recovery after photobleaching indicates a peptide diffusivity that is twice as high in actively formed condensates consistent with their loosely packed internal structure. This study contributes to linking effectively cellular active processes such as post-translational modifications to the formation and dissolution pathways of membraneless organelles, impacting other fields including synthetic biology.
SN - 2835-8279
SN - 2835-8279
ER -