Oxidation-driven synthetic molecular networks enable dynamic assembly and fluorescence modulation in living cells

Jinghui Yang; Xin Wang; Xiaoxia Wu; Yonglei Lyu; Anastassios C. Papageorgiou; Ermei Mäkilä; Jianwei Li

doi:10.1016/j.xcrp.2025.102922

Oxidation-driven synthetic molecular networks enable dynamic assembly and fluorescence modulation in living cells

Jinghui Yang
, Xin Wang
, Xiaoxia Wu
, Yonglei Lyu
, Anastassios C. Papageorgiou
, Ermei Mäkilä
, Jianwei Li^*

^*Corresponding author for this work

Turku Bioscience Centre

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Systems chemistry explores emergent properties from interacting molecular networks, although extending these systems into biologically relevant environments remains challenging. Here, we report a synthetic molecular network that functions dynamically inside living cells by responding autonomously to oxidative stimuli. The network is built from dithiol precursors that undergo oxidation-driven macrocyclization and co-assemble with an aggregation-induced emission luminogen to form fluorescent nanostructures selectively under oxidative conditions. This process is reversible, allowing repeated cycles of fluorescence modulation. By exploiting intracellular oxidation as a stimulus, the system links systems chemistry with biological complexity and enables real-time monitoring of cellular redox dynamics through fluorescence. The fluctuations in signal directly reflect oxidative levels in living cells, providing a tool for tracking redox states. Our work demonstrates adaptive molecular self-assembly in a biological context and opens opportunities for redox bioimaging, diagnostics, and therapeutics regulated by cellular oxidative environments.

Original language	English
Article number	102922
Journal	Cell Reports Physical Science
Volume	6
Issue number	11
DOIs	https://doi.org/10.1016/j.xcrp.2025.102922
Publication status	Published - 19 Nov 2025
MoE publication type	A1 Journal article-refereed

Funding

We are grateful for financial support from the National Natural Science Foundation of China ( 22161016 ), the Macau University of Science and Technology, and the Sigrid Jusélius Foundation (Senior Researcher Fellowship). J.Y. and X.W. acknowledge support from the China Scholarship Council (CSC). We thank the Turku Center for Chemical and Molecular Analytics for providing NMR and mass spectrometry, and the Electron Microscopy Laboratory (Institute of Biomedicine, University of Turku) and Biocenter Finland for TEM imaging.

Keywords

adaptive molecular networks
dynamic covalent networks
intracellular dynamic assembly
redox-responsive self-assembly
supramolecular chemistry

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10.1016/j.xcrp.2025.102922Licence: CC BY-NC-ND

https://www.utupub.fi/handle/10024/197089Licence: CC BY-NC-ND

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title = "Oxidation-driven synthetic molecular networks enable dynamic assembly and fluorescence modulation in living cells",

abstract = "Systems chemistry explores emergent properties from interacting molecular networks, although extending these systems into biologically relevant environments remains challenging. Here, we report a synthetic molecular network that functions dynamically inside living cells by responding autonomously to oxidative stimuli. The network is built from dithiol precursors that undergo oxidation-driven macrocyclization and co-assemble with an aggregation-induced emission luminogen to form fluorescent nanostructures selectively under oxidative conditions. This process is reversible, allowing repeated cycles of fluorescence modulation. By exploiting intracellular oxidation as a stimulus, the system links systems chemistry with biological complexity and enables real-time monitoring of cellular redox dynamics through fluorescence. The fluctuations in signal directly reflect oxidative levels in living cells, providing a tool for tracking redox states. Our work demonstrates adaptive molecular self-assembly in a biological context and opens opportunities for redox bioimaging, diagnostics, and therapeutics regulated by cellular oxidative environments.",

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author = "Jinghui Yang and Xin Wang and Xiaoxia Wu and Yonglei Lyu and Papageorgiou, \{Anastassios C.\} and Ermei M{\"a}kil{\"a} and Jianwei Li",

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AU - Yang, Jinghui

AU - Wang, Xin

AU - Wu, Xiaoxia

AU - Lyu, Yonglei

AU - Papageorgiou, Anastassios C.

AU - Mäkilä, Ermei

AU - Li, Jianwei

PY - 2025/11/19

Y1 - 2025/11/19

N2 - Systems chemistry explores emergent properties from interacting molecular networks, although extending these systems into biologically relevant environments remains challenging. Here, we report a synthetic molecular network that functions dynamically inside living cells by responding autonomously to oxidative stimuli. The network is built from dithiol precursors that undergo oxidation-driven macrocyclization and co-assemble with an aggregation-induced emission luminogen to form fluorescent nanostructures selectively under oxidative conditions. This process is reversible, allowing repeated cycles of fluorescence modulation. By exploiting intracellular oxidation as a stimulus, the system links systems chemistry with biological complexity and enables real-time monitoring of cellular redox dynamics through fluorescence. The fluctuations in signal directly reflect oxidative levels in living cells, providing a tool for tracking redox states. Our work demonstrates adaptive molecular self-assembly in a biological context and opens opportunities for redox bioimaging, diagnostics, and therapeutics regulated by cellular oxidative environments.

AB - Systems chemistry explores emergent properties from interacting molecular networks, although extending these systems into biologically relevant environments remains challenging. Here, we report a synthetic molecular network that functions dynamically inside living cells by responding autonomously to oxidative stimuli. The network is built from dithiol precursors that undergo oxidation-driven macrocyclization and co-assemble with an aggregation-induced emission luminogen to form fluorescent nanostructures selectively under oxidative conditions. This process is reversible, allowing repeated cycles of fluorescence modulation. By exploiting intracellular oxidation as a stimulus, the system links systems chemistry with biological complexity and enables real-time monitoring of cellular redox dynamics through fluorescence. The fluctuations in signal directly reflect oxidative levels in living cells, providing a tool for tracking redox states. Our work demonstrates adaptive molecular self-assembly in a biological context and opens opportunities for redox bioimaging, diagnostics, and therapeutics regulated by cellular oxidative environments.

KW - adaptive molecular networks

KW - dynamic covalent networks

KW - intracellular dynamic assembly

KW - redox-responsive self-assembly

KW - supramolecular chemistry

KW - dynamic covalent networks

KW - redox-responsive self-assembly

KW - adaptive molecular networks

KW - intracellular dynamic assembly

UR - https://www.scopus.com/pages/publications/105022073503

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DO - 10.1016/j.xcrp.2025.102922

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AN - SCOPUS:105022073503

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JO - Cell Reports Physical Science

JF - Cell Reports Physical Science

IS - 11

M1 - 102922

ER -

Oxidation-driven synthetic molecular networks enable dynamic assembly and fluorescence modulation in living cells

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