Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Hannes Ausserwöger - , University of Cambridge (Author)
  • Rob Scrutton - , University of Cambridge (Author)
  • Charlotte M. Fischer - , University of Cambridge (Author)
  • Tomas Sneideris - , University of Cambridge (Author)
  • Daoyuan Qian - , University of Cambridge (Author)
  • Ella de Csilléry - , University of Cambridge (Author)
  • Ieva Baronaite - , University of Cambridge (Author)
  • Kadi L. Saar - , University of Cambridge (Author)
  • Alan Z. Białek - , University of Cambridge (Author)
  • Marc Oeller - , Max Planck Institute of Biochemistry (Author)
  • Georg Krainer - , University of Cambridge, University of Graz, BioTechMed-Graz (Author)
  • Titus M. Franzmann - , Chair of Cellular Biochemistry, Biotechnology Center (Author)
  • Sina Wittmann - , Institute of Molecular Biology (IMB) (Author)
  • Juan M. Iglesias-Artola - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Gaetano Invernizzi - , Novo Nordisk A/S Pharma (Author)
  • Anthony A. Hyman - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Simon Alberti - , Chair of Cellular Biochemistry, Biotechnology Center (Author)
  • Nikolai Lorenzen - , Novo Nordisk A/S Pharma (Author)
  • Tuomas P.J. Knowles - , University of Cambridge (Author)

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

Original languageEnglish
Pages (from-to)246-257
Number of pages12
JournalNature chemistry
Volume18
Issue number2
Publication statusPublished - Feb 2026
Peer-reviewedYes

External IDs

PubMed 41612036

Keywords