Synthesis of Abiotic Supramolecular Polymers Inside Living Cells via Organocatalysis-Mediated Self-Assembly

Journal Article (2025)
Author(s)

Hucheng Wang (East China University of Science and Technology)

Ya Ting Zheng (Beijing Normal University)

Jiahao Zhang (East China University of Science and Technology)

Yuliang Gao (East China University of Science and Technology)

Jingjing Chen (East China University of Science and Technology)

Peiwen Cai (East China University of Science and Technology)

Jan H. van Esch (TU Delft - ChemE/Advanced Soft Matter)

Hui Li (Beijing Normal University)

Yiming Wang (East China University of Science and Technology)

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Research Group
ChemE/Advanced Soft Matter
DOI related publication
https://doi.org/10.1002/anie.202500998 Final published version
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Publication Year
2025
Language
English
Research Group
ChemE/Advanced Soft Matter
Bibliographical Note
Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.
Journal title
Angewandte Chemie - International Edition
Issue number
21
Volume number
64
Article number
e202500998
Downloads counter
191
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Abstract

Cells execute mesmerizing functions using supramolecular polymers (SPs) formed through the self-assembly of biological precursors. Integration of the vast array of synthetic SPs with living cells would offer a powerful way to remold cellular functions and bridge the gap between synthetic materials and the biological realm, yet remains a challenge because of the lack of robust abiotic SP systems that can be triggered to self-assemble inside cells. Here, we report how fully abiotic SPs can be synthesized inside living cells via an organocatalysis-responsive self-assembly strategy, and how the in situ-generated SPs are capable of interfering and can interfere with cellular functions. The incorporation of a nucleophilic organocatalyst (CAT) into living cells accelerates the intracellular conversion of hydrazide (H) and aldehyde-derived precursors (A) to hydrazone-based monomers (HA3) that locally self-assemble into SPs. Interestingly, the in situ-generated SPs possess ignorable effects on cell viability and proliferation but remarkably hinder cell migration. Furthermore, the presence of SPs is found to retard intracellular diffusion and alter the organization of the actin cytoskeleton, both of which are suggested to be responsible for the hindered cellular migration. In considering the vastly wide range of synthetic SPs, tremendous non-natural cellular functionalities can be obtained by in situ-synthesizing SPs.

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