Mechano-crosstalk between living and artificial cells

Xiaolei Yu, Vincent Mukwaya, Li Wang, Weili Zhao, Stephen Mann () and Hongjing Dou ()
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Xiaolei Yu: Shanghai Jiao Tong University
Vincent Mukwaya: Shanghai Jiao Tong University
Li Wang: Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Weili Zhao: Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Stephen Mann: Shanghai Jiao Tong University
Hongjing Dou: Shanghai Jiao Tong University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63581-1

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