2. Academic Validation
  3. Coacervate droplets as pH-regionalized protocells

Coacervate droplets as pH-regionalized protocells

  • Nat Commun. 2026 Feb 2;17(1):2252. doi: 10.1038/s41467-026-68980-6.
Chong Wang 1 2,  Zhonglin Fang 2,  Linyi Zhang 2,  Yuanjin Zhao 1,  Luoran Shang 3 4
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
  • 2 Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • 3 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China. [email protected].
  • 4 Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China. [email protected].
PMID: 41629347 DOI: 10.1038/s41467-026-68980-6
Abstract

The mechanisms governing pH regulation in membrane-less organelles (MLOs) are essentially different from those relying on membrane proteins, yet it remains poorly understood due to the difficulty in directly controlling the conditions across the MLOs interface. Here, we develop a coacervate-based, in vitro model to investigate how liquid-liquid phase separation (LLPS) could contribute to pH regulation in MLOs. We construct peptide-based coacervate droplets using microfluidics and find that charged Polymers within the coacervates help create uneven H+/OH- distributions, resulting in pH-regionalized microenvironments similar to the nucleolus. More interestingly, such a pH difference weakens or even disappears following the destruction of LLPS, a phenomenon observed in both nucleolus and coacervate droplets. Based on these findings, we demonstrate the ability to finely tune the local pH of the coacervate droplets over a wide range by incorporating Enzymes, which can drive and control cascade reactions, and perform basic Molecular Biology operations such as polymerase chain reaction (PCR) and in vitro transcription and translation reaction (IVTT). This study highlights the role of LLPS in pH modulation within MLOs and provides insights into the potential of coacervates as protocells for broader applications.

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