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  • Featured in Physics
  • Open Access

Enzymatically Driven Remodeling of Growth Kinetics and Internal Structure in Biomolecular Condensates

Tamizhmalar Sundararajan1, Matteo Boccalini2, Roméo Suss1,3, Sandrine Mariot1, Emerson R. Da Silva1,4, Fernando C. Giacomelli1,5, Austin Hubley6, Theyencheri Narayanan6, Alessandro Barducci2 et al.

Guillaume Tresset1,*

  • *Contact author: guillaume.tresset@cnrs.fr
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PRX Life 4, 043001 – Published 8 October, 2026

DOI: https://doi.org/10.1103/n8nd-sgs6

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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This article appears in the following collection:

Collection on Physics of Biomolecular Condensates

From the fundamentals of phase separation, dynamics and structure of condensates in biological settings, to advanced imaging methods, this special collection presented by PRX Life showcases exciting and timely work on the physics of biomolecular condensates.

This Invited Collection is coordinated by PRX Life Associate Editor Christoph Weber, in consultation with Jerelle Joseph, Simon Alberti, and Tanja Mittag. Every article published in this collection underwent a rigorous peer review process, adhering to the same high standards applied to all papers handled by the journal. The PRX Life editorial team managed the peer review and made all editorial decisions.

synopsis

Enzymes Strongly Affect Sequestered Biomolecules

Published 8 October, 2026

Regions within a cell in which biomolecules are concentrated, called condensates, form different structures when enzymes are involved, according to experiments.

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PRX Life 4, 043001– Published 8 October, 2026
  • Received 22 December 2025
  • Accepted 7 August 2026
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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