Cytoplasmic Abundant Heat-Soluble Proteins from Tardigrades Protect Synthetic Cells Under Stress

Xi, Y.; Mao, J.; Chen, S. J.; Moghimianavval, H.; Lee, Y. J.; Huang, A. J.; Zhou, D.; Xu, A.; Fu, K.; Adera, S.; Ferguson, A. L.; Liu, A. P.

doi:10.1101/2025.08.07.669088

bioRxiv · 10.1101/2025.08.07.669088

Cytoplasmic Abundant Heat-Soluble Proteins from Tardigrades Protect Synthetic Cells Under Stress

Xi, Y.·Mao, J.·Chen, S. J.·Moghimianavval, H.·Lee, Y. J.·Huang, A. J.·Zhou, D.·Xu, A.·Fu, K.·Adera, S.·Ferguson, A. L.·Liu, A. P.

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Abstract

Cytoplasmic abundant heat-soluble (CAHS) proteins, a stress-responsive intrinsically disordered protein from tardigrades, have been discovered to form gel-like networks providing structural support during dehydration, thus enabling anhydrobiosis. However, the mechanism by which CAHS proteins protect the dehydrating cellular membrane remains enigmatic. Using giant unilamellar vesicles (GUVs) as a model membrane system, we show that encapsulated CAHS12 undergoes a reversible structural transformation that reinforces membrane integrity and preserves encapsulated components, mimicking natural anhydrobiosis. CAHS12-containing GUVs demonstrated stability for weeks and mechanical robustness under dehydration, elevated temperature, and osmotic stresses. Molecular simulations suggest that CAHS12 forms a filamentous network within the vesicle lumen that mitigates membrane collapse and preserves compartmental architecture. Synthetic cells with cell-free transcription-translation capabilities withstand desiccation and recover biochemical activities, akin to the tun state of the tardigrade. This discovery opens up synthetic cell applications in bioengineering, cold-chain-independent biomanufacturing, and adaptive biointerfaces.

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Xi, Y., Mao, J., Chen, S. J., Moghimianavval, H., Lee, Y. J., Huang, A. J., Zhou, D., Xu, A., Fu, K., Adera, S., Ferguson, A. L., Liu, A. P.. 2025-08-07. Cytoplasmic Abundant Heat-Soluble Proteins from Tardigrades Protect Synthetic Cells Under Stress. https://doi.org/10.1101/2025.08.07.669088

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