Liquid-liquid phase separation-boosted transmembrane delivery in interactive protocell communities

Yan Huang, Haixu Chen, Xin Qiao, Shangsong Li, Xiaoliang Wang (), Xiaoman Liu and Xin Huang ()
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Yan Huang: Harbin Institute of Technology
Haixu Chen: Harbin Institute of Technology
Xin Qiao: Harbin Institute of Technology
Shangsong Li: Harbin Institute of Technology
Xiaoliang Wang: Harbin Institute of Technology
Xiaoman Liu: Harbin Institute of Technology
Xin Huang: Harbin Institute of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Stress stimulation-mediated liquid-liquid phase separation is a key activity in living organisms, but its biophysical characteristics are poorly understood. Here, we report a UV-light stress stimulation behaviour in a binary community of synthetic protocells of condensates and proteinosomes, showing that condensates could behave like Condensate Pumps to enable a stepwise controlled transmembrane mass transfer regardless of the permeability barrier of proteinosomes. The stimulation mechanism of interfacial tension-induced proteinosome deformation and transient high osmotic pressure arisen by the dissociation of condensate is proposed. Accordingly, under UV-light stress stimulation, unexpected characteristics could be triggered by transmembrane pumping oversized biomacromolecules into proteinosomes including liquid-liquid reentrant phase separation, DNA unwinding, and protein synthesis. Therefore, our results not only reveal unique physical principles and potential characteristics of macromolecular assemblies at droplet-membrane interface but also highlight a pathway for transmembrane transport of biomacromolecules which is anticipated to serve as a powerful technique to inducing higher-order behaviour in synthetic protocells community.

Date: 2025
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DOI: 10.1038/s41467-025-60541-7

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