近日，英国剑桥大学Knowles, Tuomas P. J.团队揭示了生物分子凝聚物通过电荷中和维持pH梯度在平衡状态。2026年1月29日，《自然-化学》杂志发表了这一成果。

电化学梯度对细胞功能至关重要，传统上认为需要主动转运蛋白跨膜形成。

研究组发现，生物分子凝聚系统（通常称为凝聚体）无需外部能量输入即可维持pH梯度。通过微滴平台在微米尺度上研究单个凝聚体，他们揭示了其致密相pH会向静电斥力最小的条件偏移。研究组表明，蛋白质凝聚体能驱动显著的碱性与酸性梯度，这些梯度可通过组分调节，并能延伸至复杂结构体系，同时维持多个独特的pH环境。

通过对人类蛋白质组凝聚体网络的计算机模拟表征，研究组进一步揭示了自然界中相分离现象可能产生的广泛电化学特性，同时将细胞内凝聚体pH梯度与复杂的生物分子组成相关联。综上所述，相分离的自发特性塑造了独特的pH微环境，从而形成了一种调控机制，可用于调节生命系统与人工系统中的生物化学活性。

附：英文原文

Title: Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization

Author: Ausserwger, Hannes, Scrutton, Rob, Fischer, Charlotte M., Sneideris, Tomas, Qian, Daoyuan, de Csillry, Ella, Baronaite, Ieva, Saar, Kadi L., Biaek, Alan Z., Oeller, Marc, Krainer, Georg, Franzmann, Titus M., Wittmann, Sina, Iglesias-Artola, Juan M., Invernizzi, Gaetano, Hyman, Anthony A., Alberti, Simon, Lorenzen, Nikolai, Knowles, Tuomas P. J.

Issue&Volume: 2026-01-29

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.

DOI: 10.1038/s41557-025-02039-9

Source: https://www.nature.com/articles/s41557-025-02039-9