Gear-like MOF microrobots for single cell mechanotransduction of microvilli

Code associated with our paper is available at https://github.com/alfredyang93/Demo-datasets.

1. Zhang, Y. & Habibovic, P. Delivering mechanical stimulation to cells: state of the art in materials and devices design. Adv. Mater. 34, e2110267 (2022).

   Google Scholar 

2. Humphrey, J. D., Dufresne, E. R. & Schwartz, M. A. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15, 802–812 (2014).

   Google Scholar 

3. Lin, Y. C. et al. Force-induced conformational changes in PIEZO1. Nature 573, 230 (2019).

   Google Scholar 

4. Savadipour, A. et al. Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes. Proc. Natl. Acad. Sci. Usa. 120, e2221958120 (2023).

   Google Scholar 

5. Andreu, I. et al. The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening. Nat. Commun. 12, 4229 (2021).

   Google Scholar 

6. Dasgupta, I. & McCollum, D. Control of cellular responses to mechanical cues through YAP/TAZ regulation. J. Biol. Chem. 294, 17693–17706 (2019).

   Google Scholar 

7. Elosegui-Artola, A. et al. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell 171, 1397 (2017).

   Google Scholar 

8. Korkmazhan, E. & Dunn, A. R. The membrane-actin linker ezrin acts as a sliding anchor. Sci. Adv. 8, eabo2779 (2022).

   Google Scholar 

9. Du, Z. et al. Mechanosensory function of microvilli of the kidney proximal tubule. Proc. Natl. Acad. Sci. Usa. 101, 13068–13073 (2004).

   Google Scholar 

10. Cai, E. et al. Visualizing dynamic microvillar search and stabilization during ligand detection by T cells. Science 356, eaal3118 (2017).

    Google Scholar 

11. Weinbaum, S., Guo, P. & You, L. D. A new view of mechanotransduction and strain amplification in cells with microvilli and cell processes. Biorheology 38, 119–142 (2001).

    Google Scholar 

12. Iyer, S., Gaikwad, R. M., Subba-Rao, V., Woodworth, C. D. & Sokolov, I. Atomic force microscopy detects differences in the surface brush of normal and cancerous cells. Nat. Nanotechnol. 4, 389–393 (2009).

    Google Scholar 

13. Schneeberger, K. et al. An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking. Proc. Natl. Acad. Sci. USA. 112, 12408–12413 (2015).

    Google Scholar 

14. Delon, L. C. et al. A systematic investigation of the effect of the fluid shear stress on Caco-2 cells towards the optimization of epithelial organ-on-chip models. Biomaterials 225, 119521 (2019).

    Google Scholar 

15. Miura, S., Sato, K., Kato-Negishi, M., Teshima, T. & Takeuchi, S. Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6. Nat. Commun. 6, 8871 (2015).

    Google Scholar 

16. Aramesh, M. et al. Nanoconfinement of microvilli alters gene expression and boosts T cell activation. Proc. Natl. Acad. Sci. USA. 118, e2107535118 (2021).

    Google Scholar 

17. Luo, M., Feng, Y., Wang, T. & Guan, J. Micro-/nanorobots at work in active drug delivery. Adv. Funct. Mater. 28, 1706100 (2018).

    Google Scholar 

18. Li, J. X., De Avila, B. E. F., Gao, W., Zhang, L. F. & Wang, J. Micro/nanorobots for biomedicine: delivery, surgery, sensing, and detoxification. Sci. Robot. 2, eaam6431 (2017).

    Google Scholar 

19. Gultepe, E. et al. Biopsy with thermally-responsive untethered microtools. Adv. Mater. 25, 514–519 (2013).

    Google Scholar 

20. Wu, Z. et al. A swarm of slippery micropropellers penetrates the vitreous body of the eye. Sci. Adv. 4, eaat4388 (2018).

    Google Scholar 

21. Gao, Y. et al. Magnetically manipulated optoelectronic hybrid microrobots for optically targeted non-genetic neuromodulation. Adv. Mater. 36, 2305632 (2024).

    Google Scholar 

22. Lin, Z. et al. Magnetically actuated peanut colloid motors for cell manipulation and patterning. ACS Nano 12, 2539–2545 (2018).

    Google Scholar 

23. Chen, W. J. et al. Recent progress of micro/nanorobots for cell delivery and manipulation. Adv. Funct. Mater. 32, 2110625 (2022).

    Google Scholar 

24. Gao, Y. X. et al. Template-guided silicon micromotor assembly for enhanced cell manipulation. Angew. Chem. 63, e202405895 (2024).

    Google Scholar 

25. Zhou, H. J., Mayorga-Martinez, C. C., Pané, S., Zhang, L. & Pumera, M. Magnetically driven micro and nanorobots. Chem. Rev. 121, 4999–5041 (2021).

    Google Scholar 

26. Cao, Y. et al. Magnetic continuum robot with modular axial magnetization: design, modeling, optimization, and control. IEEE Trans. Rob. 41, 1513–1532 (2025).

    Google Scholar 

27. Liu, C. et al. Site-specific growth of MOF-on-MOF heterostructures with controllable nano-architectures: beyond the combination of MOF analogues. Chem. Sci. 11, 3680–3686 (2020).

    Google Scholar 

28. Bergert, M. et al. Confocal reference free traction force microscopy. Nat. Commun. 7, 12814 (2016).

    Google Scholar 

29. Guo, J., Wang, Y., Sachs, F. & Meng, F. Actin stress in cell reprogramming. Proc. Natl. Acad. Sci. Usa. 111, E5252–E5261 (2014).

    Google Scholar 

30. Yang, J. et al. Photo-tunable hydrogels reveal cellular sensing of rapid rigidity changes through the accumulation of mechanical signaling molecules. Cell Stem Cell 32, 121–136 (2025).

    Google Scholar 

31. Zhang, M. et al. Cell mechanical responses to subcellular perturbations generated by ultrasound and targeted microbubbles. Acta Biomater. 155, 471–481 (2023).

    Google Scholar 

32. Yuan, F., Yang, C. & Zhong, P. Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow. Proc. Natl. Acad. Sci. USA. 112, E7039–E7047 (2015).

    Google Scholar 

33. Yang, T. et al. Microwheels on microroads: enhanced translation on topographic surfaces. Sci. Robot. 4, eaaw9525 (2019).

    Google Scholar 

34. Chien, S. Molecular and mechanical bases of focal lipid accumulation in arterial wall. Prog. Biophys. Mol. Biol. 83, 131–151 (2003).

    Google Scholar 

35. Shi, Z., Graber, Z. T., Baumgart, T., Stone, H. A. & Cohen, A. E. Cell membranes resist flow. Cell 175, 1769–1779 (2018).

    Google Scholar 

36. Katta, S., Krieg, M. & Goodman, M. B. Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu. Rev. Cell Dev. Biol. 31, 347–371 (2015).

    Google Scholar 

Download references

Authors and Affiliations

1. Sauvage Laboratory for Smart Materials, School of Integrated Circuits, Harbin Institute of Technology (Shenzhen), Shenzhen, China

   Xiaoxia Liu, Peng Wang, Dongdong Jin & Xing Ma

2. School of Biomedical Engineering and Medical Imaging, Army Medical University, Chongqing, China

   Xiaoxia Liu

3. Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China

   Yong Wang & Jinhong Guo

4. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China

   Lin Lin & Xiaohui Yan

5. School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai, China

   Ning Liu

6. School of Computing and Artificial Intelligence, Southwest Jiaotong University, Chengdu, China

   Zihao Yang

7. School of Automation and Intelligent Sensing, Shanghai Jiao Tong University, Shanghai, China

   Jinhong Guo

Contributions

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.

Corresponding authors

Correspondence to Yong Wang, Dongdong Jin or Xing Ma.

Competing interests

The authors declare no competing interests.

Peer review information

Nature Communications thanks Pierre Bongrand and Jianguo Guan for their contribution to the peer review of this work. [A peer review file is available].

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions