Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization

Read full text
Authors: Hannes Ausserwöger, Rob Scrutton, Charlotte M. Fischer, Tomas Šneideris, Daoyuan Qian, Ella de Csilléry, Ieva Baronaite, Kadi L. Saar, Alan Z. Białek, Marc Oeller, Georg Krainer, Titus M. Franzmann
+7 more Sina Wittmann, Juan M. Iglesias‐Artola, Gaetano Invernizzi, Anthony A. Hyman, Simon Alberti, Nikolai Lorenzen, Tuomas P. J. Knowles
Cited by: 23
References: 72

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.

Fields of Study & Subjects

Biotin and Related Studies Nanopore and Nanochannel Transport Studies Molecular Junctions and Nanostructures

Publication details

Journal / source
Nature Chemistry
Publisher
Springer Science and Business Media LLC
Volume
18
Issue
2
Pages
246–257
Publication date
29 January 2026
Language
EN