Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Hannes Ausserwöger - , University of Cambridge (Autor:in)
  • Rob Scrutton - , University of Cambridge (Autor:in)
  • Charlotte M. Fischer - , University of Cambridge (Autor:in)
  • Tomas Sneideris - , University of Cambridge (Autor:in)
  • Daoyuan Qian - , University of Cambridge (Autor:in)
  • Ella de Csilléry - , University of Cambridge (Autor:in)
  • Ieva Baronaite - , University of Cambridge (Autor:in)
  • Kadi L. Saar - , University of Cambridge (Autor:in)
  • Alan Z. Białek - , University of Cambridge (Autor:in)
  • Marc Oeller - , Max Planck Institute of Biochemistry (Autor:in)
  • Georg Krainer - , University of Cambridge, Karl-Franzens-Universität Graz, BioTechMed-Graz (Autor:in)
  • Titus M. Franzmann - , Professur für Zelluläre Biochemie, Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Sina Wittmann - , Institute of Molecular Biology (IMB) (Autor:in)
  • Juan M. Iglesias-Artola - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Gaetano Invernizzi - , Novo Nordisk A/S Pharma (Autor:in)
  • Anthony A. Hyman - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Simon Alberti - , Professur für Zelluläre Biochemie, Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Nikolai Lorenzen - , Novo Nordisk A/S Pharma (Autor:in)
  • Tuomas P.J. Knowles - , University of Cambridge (Autor:in)

Abstract

Electrochemical gradients are essential to the functioning of cells and form across membranes using active transporters. Here we show in contrast that condensed biomolecular systems—often termed condensates—sustain pH gradients without any external energy input. By studying individual condensates on the micrometre scale using a microdroplet platform, we reveal dense-phase pH shifts towards conditions of minimal electrostatic repulsion. We demonstrate that protein condensates can drive substantial alkaline and acidic gradients, which are compositionally tunable and can extend to complex architectures sustaining multiple unique pH conditions simultaneously. Through in silico characterization of human proteomic condensate networks, we further highlight potential wide-ranging electrochemical properties emerging from condensation in nature, while correlating intracellular condensate pH gradients with complex biomolecular composition. Together, the emergent nature of condensation shapes distinct pH microenvironments, thereby creating a regulatory mechanism to modulate biochemical activity in living and artificial systems. (Figure presented.)

Details

OriginalspracheEnglisch
Seiten (von - bis)246-257
Seitenumfang12
FachzeitschriftNature chemistry
Jahrgang18
Ausgabenummer2
PublikationsstatusVeröffentlicht - Feb. 2026
Peer-Review-StatusJa

Externe IDs

PubMed 41612036