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NANOG Assembles into Self-Limiting Aging Micelles That Drive a Sol-Gel Transition and Modulate DNA Dynamics

Amandine Hong-Minh1,2,*, Yair Augusto Gutiérrez Fosado2,*, Abbie Guild3,1,4, Nicholas Mullin1,4, Laura Spagnolo3, Ian Chambers1,4,†, and Davide Michieletto2,5,6,‡

  • *These authors contributed equally to this work.
  • †Contact author: ichambers@ed.ac.uk
  • ‡Contact author: davide.michieletto@ed.ac.uk
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Phys. Rev. Lett. 137, 018402 – Published 30 June, 2026

DOI: https://doi.org/10.1103/sj9b-dcwd

Abstract

Proteins and nucleic acids form non-Newtonian liquids with complex rheological properties that contribute to their function in vivo. Here, we investigate the rheology of the transcription factor NANOG, a key protein to maintain embryonic stem cell pluripotency. We find that, at high concentrations, NANOG forms macroscopic aging gels that are dependent on its intrinsically disordered domain. By combining molecular dynamics simulations, mass photometry, and cryo-EM, we also discover that—in contrast to unbounded condensates formed by other intrinsically disordered proteins—NANOG forms self-limiting micelles with exposed DNA-binding domains. We show that these micelles can stabilize DNA entanglements and, in turn, modulate DNA dynamics. Based on our findings, we conjecture that NANOG may contribute to regulate gene expression by creating local gel-like environments that restrict genome dynamics and that its aging may ingrain mechanical memory in gene regulatory networks.

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Phys. Rev. Lett. 137, 018402– Published 30 June, 2026
  • Received 1 December 2025
  • Accepted 27 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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