2. Academic Validation
  3. Mechano-crosstalk between living and artificial cells

Mechano-crosstalk between living and artificial cells

  • Nat Commun. 2025 Sep 29;16(1):8582. doi: 10.1038/s41467-025-63581-1.
Xiaolei Yu 1,  Vincent Mukwaya 1,  Li Wang 2,  Weili Zhao 2,  Stephen Mann 3 4 5,  Hongjing Dou 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China.
  • 2 Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China. s.mann@bristol.ac.uk.
  • 4 Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, UK. s.mann@bristol.ac.uk.
  • 5 Max Planck-Bristol Centre for Minimal Biology, School of Chemistry, University of Bristol, Bristol, UK. s.mann@bristol.ac.uk.
  • 6 State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China. hjdou@sjtu.edu.cn.
PMID: 41022765 DOI: 10.1038/s41467-025-63581-1
Abstract

The mechanisms underlying the probing and response of cells to direct cell-presented mechanical signals generated in the local microenvironment are important controllers of diverse cell behaviours. Here we construct a model artificial pathogen cell with the similar compartmentalization architecture and same range of tunable rigidity as found in natural cells. By incubating the artificial cells with macrophages, we investigate the mechanisms of mechano-crosstalk between living cells and model protocells. We show that macrophages are equipped with distinct pseudopodia that facilitate the probing of cell-presented mechanical signals. Increasing the rigidity of the artificial pathogen cells enhances the proinflammatory polarization of the macrophages by promoting the docking of the mechanosensitive molecular clutch, actin assembly, and pseudopodia extension. The relationship between cell morphology and functional plasticity involves a mechano-transduction axis including artificial cell rigidity, pseudopodia, and macrophage inflammatory response. Taken together, our model protocells provide a new platform to decouple cell-presented mechanical signals and highlight their role in governing protocell-living cell mechano-crosstalk.

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