Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization
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.
Authors
- Anthony A. Hyman (ORCID: https://orcid.org/0000-0003-3664-154X)
- Simon Alberti (ORCID: https://orcid.org/0000-0003-4017-6505)
- Georg Krainer (ORCID: https://orcid.org/0000-0002-9626-7636)
- Kadi L. Saar (ORCID: https://orcid.org/0000-0002-5926-3628)
- Daoyuan Qian (ORCID: https://orcid.org/0000-0002-8539-3346)
- Titus M. Franzmann (ORCID: https://orcid.org/0000-0002-4281-7209)
- Alan Z. Białek
- Ieva Baronaite
- Marc Oeller
- Nikolai Lorenzen
- Gaetano Invernizzi
- Ella de Csilléry
- Tuomas P. J. Knowles
- Hannes Ausserwöger
Institutions
- University of Graz (AT)
- Novo Nordisk (Denmark) (DK)
- University of Cambridge (GB)
- BioTechMed-Graz (AT)
- Center for Systems Biology Dresden (DE)
- Max Planck Institute of Biochemistry (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Institute of Molecular Biology (DE)
- Technische Universität Dresden (DE)
Publication Details
- Journal
- Nature Chemistry
- Published
- 2026-01-29
- DOI
- https://doi.org/10.1038/s41557-025-02039-9
- Citations
- 2
- Primary Topic
- Biotin and Related Studies
- Type
- article
- Field-Weighted Citation Impact
- 46.14