Abstract
Cellular mechanotransduction, mediated by specialized structures such as microvilli, regulates processes ranging from tissue homeostasis to disease progression. Existing tools for microvilli-specific biomechanical intervention suffer from limited spatiotemporal precision and non-physiological constraints, restricting mechanistic studies and targeted therapies. Here, we develop a magnetically driven gear-like metal-organic framework microrobot (MOFbot) for programmable mechanical manipulation of single-cell microvilli. MOFbots are fabricated through epitaxial growth of heterogeneous MOF structures followed by deposition of Ni/Au nanofilms. Under a rotating magnetic field, they perform rolling and obstacle negotiation. Their rotating gear structure entangles microvilli, exerting quantified pulling forces via Förster resonance energy transfer and traction force microscopy. This mechanical stimulation triggers intracellular calcium influx and enhanced focal adhesion kinase phosphorylation, indicating mechanotransduction pathway activation. Consequently, rotating MOFbots increase membrane permeability, enabling on-demand transmembrane delivery of therapeutics into targeted single cells. This work establishes a targeted cellular mechanomodulation strategy and informs future micro/nanorobotic biomedical designs.
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Data availability
The data generated or analysed during this study are included in this published article/Supplementary Information/Source Data file. Source data is available for Figs.1d–g, 2c, 2d, 2f, 2i, 2k, 3e–g, 4c, 4d, 4h, 4i, 5c–f, 5h, 6d, 6f–h and Supplementary Figs. 3, 4, 6, 8, 10b, 12b, 12c, 13b, 13c, 15b, 19c, 20b, 21, 22a, 22b, 24 in the associated source data file. The raw data generated in this study have also been deposited in the Zenodo database under accession code [10.5281/zenodo.18495219]. Source data are provided with this paper.
Code availability
Code associated with our paper is available at https://github.com/alfredyang93/Demo-datasets.
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Acknowledgements
This work was supported by Shenzhen Science and Technology Program (RCJC20231211090000001 to X.M.), Shenzhen Medical Research Fund (A2403068 to D.J.), Shenzhen Science and Technology Program (GXWD20231129101105001 to X.M., KJZD20231023100302006 to D.J.), National Natural Science Foundation of China (52472280 to D.J., 82402730 to Y.W.), Macau Foundation for Development of Sicence and Technology (0008/2024/RIA1 to X.M.), China Postdoctoral Science Foundation (2024M763882 to X.L.).
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X.L. synthesized and characterized the MOFbots, analyzed the interaction between MOFbots and cellular microvilli, and wrote the paper. Y.W. was responsible for video recording of the MOFbots and data analysis. L.L. simulated the flow field around the MOFbots. N.L. simulated the interaction between the gear-like MOFbot and cellular microvilli. Z.Y. analyzed the distribution of gear-like MOFbots within cellular microvilli using the Unet + + network model. P.W. analyzed the cell substrate deformation induced by the MOFbot. X.Y. and J.G. revised the manuscript. Y.W., D.J. and X.M. conceived the initial idea, supervised the project, and edited the paper.
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Liu, X., Wang, Y., Lin, L. et al. Gear-like MOF microrobots for single cell mechanotransduction of microvilli. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70052-8
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DOI: https://doi.org/10.1038/s41467-026-70052-8
