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Light-fuelled growth dynamics and structural transition of synthetic protocells

Nature Synthesis volume 4, pages 1359–1368 (2025)Cite this article

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Abstract

A hallmark of life is its capacity to grow and make changes in response to specific conditions, which drives adaptation and variation within populations. Replicating this ability in artificial systems marks a significant milestone in creating lifelike behaviours and probing the origin of life. Here we present an adaptive supramolecular system that exhibited complex growth and phase behaviours driven by the interplay between external environmental factors (light input) and intrinsic chemical activity. This process is powered by light-activated bond scission of strained cyclic disulfides in monomers, followed by the formation of diverse oligomers with linear disulfide linkages. Through self-organization, the information of chemical reactions is translated into protocellular growth and structural transition by coupling supramolecular aggregation and liquid–liquid phase separation. Our findings highlight the emergence of chemical complexity and the formation of cell-like structures from simple molecular systems, offering insights into the mechanisms of self-organization and compartmentalization, which are crucial to understanding the origin of life.

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Fig. 1: Light-fuelled molecular and protocellular systems.
Fig. 2: Reactivity of linear and cyclic disulfides.
Fig. 3: Light-triggered protocell growth and structural transition (case II).
Fig. 4: Light-activated protocell dynamics (case III).
Fig. 5: Inhibition and termination of protocell growth.

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Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Information. Source data for Figs. 2–5 are provided with this paper.

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Acknowledgements

We thank the National Natural Science Foundation of China (number 22172007 to Y.L. and number T2425001 to Y.Q.), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (number 52221006 to Y.L.), the Strategic Priority Research Program of the Chinese Academy of Sciences (number XDB0480000 to Y.Q.) and the Fundamental Research Funds for the Central Universities (number buctrc202015 to Y.L.) for financial support.

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Authors and Affiliations

  1. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China

    Ke Shi, Peiyong Song & Yiyang Lin

  2. MediCity Research Laboratory, University of Turku, Turku, Finland

    Jianwei Li

  3. Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

    Yan Qiao

  4. University of Chinese Academy of Sciences, Beijing, China

    Yan Qiao

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  1. Ke Shi
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Contributions

Y.L. led the project. K.S. and P.S. performed the experiments. K.S. and Y.L. conceived the experiments. K.S., P.S., J.L., Y.Q. and Y.L. analysed the data and wrote the manuscript. All authors discussed the results and have given approval to the final version of the manuscript.

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Correspondence to Yiyang Lin.

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Nature Synthesis thanks Job Boekhoven, Jianbo Liu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Thomas West, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information (download PDF )

Experimental details, Supplementary sections 1–3, Figs. 1–37.

Reporting Summary (download PDF )

Supplementary Video 1 (download MP4 )

A macroscopic video shows an A/B solution (molar ratio of 5:5, total concentration of 5 mM, pH 7.5) turns cloudy as irradiated by 365 nm UV light, indicating the light-triggered formation of coacervate droplets (5 seconds off, 10 seconds on).

Supplementary Video 2 (download AVI )

A fluorescence microscopy video captures the coacervation process in an A/B solution (molar ratio of 5:5, total concentration of 5 mM, pH 7.5) under UV light illumination from the microscope. Green fluorescent HPTS was doped into the coacervate droplets for imaging, and the video shows the continuous growth and coalescence of coacervate droplets as they were exposed to the UV-light.

Supplementary Video 3 (download AVI )

An optical microscopy video demonstrates the coacervation process in an A/B solution ([molar ratio of 5:5, total concentration of 5 mM, pH 7.5) under UV light illumination from the microscope. The video reveals the continuous growth and coalescence of coacervate droplets as the solution was exposed to the UV-light.

Supplementary Video 4 (download MP4 )

A macroscopic video shows a progression where the solution changed from transparent to turbid, and then back to transparent. The increase in turbidity was attributed to the formation of coacervate droplets induced by 365 nm UV light (5 seconds off, 10 seconds on) in an A/B solution (molar ratio of 6:4, total concentration of 5 mM, pH 7.5).

Supplementary Video 5 (download AVI )

A fluorescence microscopy video captures the UV light-triggered dynamics of the vacuolation–collapse cycles in an A/B solution (molar ratio of 6:4, total concentration of 5 mM, pH 7.5). The video shows the formation and subsequent collapse of vacuoles within the coacervate structures as the solution was exposed to UV light. This process was repeated upon continuous UV light illumination.

44160_2025_844_MOESM8_ESM.avi (download AVI )

Supplementary Video 6 A fluorescence microscopy video captures the degradation of coacervate droplets upon the addition of glucose (10 mM). The coacervates, loaded with glucose oxidase (0.1 mg·mL⁻¹, 22.3 U·mL⁻¹), catalysed the oxidation of glucose into gluconic acid using oxygen. This reaction ultimately generated hydrogen peroxide, which oxidized and cleaved the disulfide bonds, resulting in the breakdown of the coacervate structures. The coacervate droplets were prepared from A/B solution (molar ratio of 5:5, total concentration of 5 mM, pH 7.5) after UV-light irradiation.

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Shi, K., Song, P., Li, J. et al. Light-fuelled growth dynamics and structural transition of synthetic protocells. Nat. Synth 4, 1359–1368 (2025). https://doi.org/10.1038/s44160-025-00844-1

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