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Power in numbers: Emergent thermodynamic and kinetic cooperativity from biomolecular condensate growth

Caleb Huang and B. Montgomery Pettitt*

  • *Contact author: mpettitt@utmb.edu
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APS Open Sci. 1, 000042 – Published 17 June, 2026

DOI: https://doi.org/10.1103/kbfb-d5nk

Abstract

Biomolecular condensates provide a platform to modulate intracellular chemical reaction efficiency, yet how condensate size and sequence dependence are related to solubility and relaxation kinetics remains unsettled. All-atom simulations of model glycine-rich pentapeptides spanning nearly 2 orders of magnitude in aggregate size were used to connect observations of microscopic interactions among intrinsically disordered proteins and water to mesoscopic laws of condensed matter physics. The models used here show that growth induces two forms of cooperativity. Thermodynamic cooperativity lowers apparent solubility with increasing radius, which is consistent with the Ostwald-Freundlich equation. The characteristic radius in the equation marks a significant reduction in the change in solubility with increased radius. This coincides with the formation of a dense inner core of peptides that traps a subpopulation of waters. Kinetic cooperativity slows peptide exchange with increasing radius. The peptide turnover rate for the condensate in terms of survival probability was characterized. The peptide survival curves for different sized condensates and sequences follow a bifurcated Kohlrausch-Williams-Watts stretched-exponential model, which is consistent with short-range van der Waals forces dominating peptide retention at the condensate-water interface, while long-range electrostatic forces dominate peptide properties deeper within the core. Our model condensates exhibit viscoelastic properties different from Newtonian fluids like water. Our findings underscore the need to incorporate cooperative effects into biophysical models for condensates.

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APS Open Sci. 1, 000042– Published 17 June, 2026
Vol. 1
  • Received 17 October 2025
  • Revised 12 May 2026
  • Accepted 26 May 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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