Cited by 0Supramolecular Self-Assembly in MaterialsAdvanced biosensing and bioanalysis techniquesSupramolecular Chemistry and Complexes

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Restoring intracellular homeostasis disrupted by synthetic nanoassemblies

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Abstract

Cells have evolved to defend against perturbations by maintaining their intrinsic homeostasis to survive. However, no intrinsic pathway exists for them to expel new-to-biology synthetic nanostructures. Here we establish crosstalk between supramolecular transformations and genetic responses, achieving programmable influx–efflux cycles of nanoassemblies in living bacterial cells to restore redox and energy homeostasis. Specifically, a model photosensitizer–peptide conjugate undergoes multiple redox cycles between methionine and methionine sulfoxide (MetO), resulting in reversible morphological transformations between nanofibers (NFs) and nanoparticles (NPs). Upon irradiation, the oxidized peptide NPs are internalized into bacteria. To counteract the perturbations caused by internalized NPs, engineered bacteria activate the expression of MetO reductases in response to photo-oxidative stress. The internalized NPs are intracellularly enzymatically reduced such that they are expelled as reduced NFs, setting the stage for subsequent cycles. The concept presented here paves the way for the interlinked network between dynamic supramolecular assemblies and cellular regulatory behaviors.

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Research works printed but not linked: 47

  1. Liu, Y. et al. Autoregulatory control of mitochondrial glutathione homeostasis. Science 382, 820–828 (2023). · DOI
  2. Luo, J., Yang, H. & Song, B. L. Mechanisms and regulation of cholesterol homeostasis. Nat. Rev. Mol. Cell Biol. 21, 225–245 (2020). · DOI · Paper page
  3. Krenkel, O. & Tacke, F. Liver macrophages in tissue homeostasis and disease. Nat. Rev. Immunol. 17, 306–321 (2017). · DOI · Paper page
  4. Pelaz, B. et al. Diverse applications of nanomedicine. ACS Nano 11, 2313–2381 (2017). · DOI · Paper page
  5. Kim, J. et al. In situ self-assembly for cancer therapy and imaging. Nat. Rev. Mater. 8, 710–725 (2023). · DOI
  6. Zhou, Z. et al. In situ assembly of platinum(II)-metallopeptide nanostructures disrupts energy homeostasis and cellular metabolism. J. Am. Chem. Soc. 144, 12219–12228 (2022). · DOI
  7. Scheinberg, D. A., Villa, C. H., Escorcia, F. E. & McDevitt, M. R. Conscripts of the infinite armada: systemic cancer therapy using nanomaterials. Nat. Rev. Clin. Oncol. 7, 266–276 (2010). · DOI
  8. Chagri, S., Ng, D. Y. W. & Weil, T. Designing bioresponsive nanomaterials for intracellular self-assembly. Nat. Rev. Chem. 6, 320–338 (2022). · DOI
  9. Pires, R. A. et al. Controlling cancer cell fate using localized biocatalytic self-assembly of an aromatic carbohydrate amphiphile. J. Am. Chem. Soc. 137, 576–579 (2015). · DOI
  10. Liu, K. et al. Light-driven eco-evolutionary dynamics in a synthetic replicator system. Nat. Chem. 16, 79–88 (2024). · DOI
  11. Mattia, E. & Otto, S. Supramolecular systems chemistry. Nat. Nanotechnol. 10, 111–119 (2015). · DOI
  12. Álvarez, Z. et al. Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury. Science 374, 848–856 (2021). · DOI
  13. Lutz, J.-F., Lehn, J.-M., Meijer, E. W. & Matyjaszewski, K. From precision polymers to complex materials and systems. Nat. Rev. Mater. 1, 16024 (2016). · DOI
  14. Grotsch, R. K. et al. Pathway dependence in the fuel-driven dissipative self-assembly of nanoparticles. J. Am. Chem. Soc. 141, 9872–9878 (2019). · DOI
  15. Boekhoven, J., Hendriksen, W. E., Koper, G. J. M., Eelkema, R. & van Esch, J. H. Transient assembly of active materials fueled by a chemical reaction. Science 349, 1075–1079 (2015). · DOI
  16. Monreal Santiago, G., Liu, K., Browne, W. R. & Otto, S. Emergence of light-driven protometabolism on recruitment of a photocatalytic cofactor by a self-replicator. Nat. Chem. 12, 603–607 (2020). · DOI
  17. Song, N. et al. In situ oxidation-regulated self-assembly of peptides into transformable scaffolds for cascade therapy. Nano Today 38, 101198 (2021). · DOI
  18. Roth, P. et al. Supramolecular assembly guided by photolytic redox cycling. Nat. Synth. 2, 980–988 (2023). · DOI
  19. Guo, J. et al. Cell spheroid creation by transcytotic intercellular gelation. Nat. Nanotechnol. 18, 1094–1104 (2023). · DOI
  20. Ren, Y. et al. Intracellular assembly of supramolecular peptide nanostructures controlled by visible light. Nat. Synth. 4, 673–683 (2025). · DOI
  21. Liu, X. et al. In situ self-sorting peptide assemblies in living cells for simultaneous organelle targeting. J. Am. Chem. Soc. 144, 9312–9323 (2022). · DOI
  22. Liu, H. & Wang, H. From cells to subcellular organelles: next-generation cancer therapy based on peptide self-assembly. Adv. Drug Deliv. Rev. 209, 115327 (2024). · DOI
  23. Wang, X. & Pu, K. Molecular substrates for the construction of afterglow imaging probes in disease diagnosis and treatment. Chem. Soc. Rev. 52, 4549–4566 (2023). · DOI
  24. Winterwerber, P., Whitfield, C. J., Ng, D. Y. W. & Weil, T. Multiple wavelength photopolymerization of stable poly(catecholamines)–DNA origami nanostructures. Angew. Chem. Int. Ed. Engl. 61, e202111226 (2022). · DOI
  25. Lim, J. C., You, Z., Kim, G. & Levine, R. L. Methionine sulfoxide reductase A is a stereospecific methionine oxidase. Proc. Natl Acad. Sci. USA 108, 10472–10477 (2011). · DOI
  26. Zhao, L. et al. Dichromophoric zinc porphyrins: filling the absorption gap between the Soret and Q bands. J. Phys. Chem. C 119, 5350–5363 (2015). · DOI
  27. Hosomizu, K. et al. Substituent effects of porphyrins on structures and photophysical properties of amphiphilic porphyrin aggregates. J. Phys. Chem. B 112, 16517–16524 (2008). · DOI
  28. Kaygisiz, K. et al. Data-mining unveils structure–property–activity correlation of viral infectivity enhancing self-assembling peptides. Nat. Commun. 14, 5121 (2023). · DOI
  29. Yamada, N., Ariga, K., Naito, M., Matsubara, K. & Koyama, E. Regulation of β-sheet structures within amyloid-like β-sheet assemblage from tripeptide derivatives. J. Am. Chem. Soc. 120, 12192–12199 (1998). · DOI
  30. Chen, Y. & Wallace, B. A. Secondary solvent effects on the circular dichroism spectra of polypeptides in non-aqueous environments:influence of polarisation effects on the far ultraviolet spectra of alamethicin. Biophys. Chem. 65, 65–74 (1997). · DOI
  31. Fry, H. C., Liu, Y., Dimitrijevic, N. M. & Rajh, T. Photoinitiated charge separation in a hybrid titanium dioxide metalloporphyrin peptide material. Nat. Commun. 5, 4606 (2014). · DOI
  32. Pham, T. C., Nguyen, V.-N., Choi, Y., Lee, S. & Yoon, J. Recent strategies to develop innovative photosensitizers for enhanced photodynamic therapy. Chem. Rev. 121, 13454–13619 (2021). · DOI · Paper page
  33. Ren, Y. et al. Supramolecular assembly in live cells mapped by real-time phasor-fluorescence lifetime imaging. J. Am. Chem. Soc. 146, 11991–11999 (2024). · DOI
  34. Frei, M. S. et al. Engineered HaloTag variants for fluorescence lifetime multiplexing. Nat. Methods 19, 65–70 (2022). · DOI
  35. Yang, Y. et al. Bacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms. Nat. Commun. 13, 1255 (2022). · DOI
  36. Ornati, E., Perrard, J., Hoffmann, T. A., Bonon, R. & Bruns, N. Bacteria-mediated intracellular radical polymerizations. J. Am. Chem. Soc. 147, 9496–9504 (2025). · DOI
  37. Ziegelhoffer, E. C. & Donohue, T. J. Bacterial responses to photo-oxidative stress. Nat. Rev. Microbiol. 7, 856–863 (2009). · DOI
  38. Rubens, J. R., Selvaggio, G. & Lu, T. K. Synthetic mixed-signal computation in living cells. Nat. Commun. 7, 11658 (2016). · DOI
  39. Winson, M. K. et al. Engineering the luxCDABE genes from Photorhabdus luminescens to provide a bioluminescent reporter for constitutive and promoter probe plasmids and mini-Tn5 constructs. FEMS Microbiol. Lett. 163, 193–202 (1998). · DOI
  40. Levine, R. L., Mosoni, L., Berlett, B. S. & Stadtman, E. R. Methionine residues as endogenous antioxidants in proteins. Proc. Natl Acad. Sci. USA 93, 15036–15040 (1996). · DOI
  41. Ezraty, B., Gennaris, A., Barras, F. & Collet, J. F. Oxidative stress, protein damage and repair in bacteria. Nat. Rev. Microbiol. 15, 385–396 (2017). · DOI
  42. Moskovitz, J. Methionine sulfoxide reductases: ubiquitous enzymes involved in antioxidant defense, protein regulation, and prevention of aging-associated diseases. Biochim. Biophys. Acta 1703, 213–219 (2005). · DOI
  43. Bender, A., Hajieva, P. & Moosmann, B. Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria. Proc. Natl Acad. Sci. USA 105, 16496–16501 (2008). · DOI
  44. Liu, X. et al. In vivo self-sorting of peptides via in situ assembly evolution. J. Am. Chem. Soc. 146, 24177–24187 (2024). · DOI
  45. Lin, Z. et al. Nanozymes modulate probiotic tryptophan metabolism to prevent Salmonella infection in mammalian models. Nat. Microbiol. 10, 3272–3289 (2025). · DOI
  46. Cubillos-Ruiz, A. et al. Engineering living therapeutics with synthetic biology. Nat. Rev. Drug Discov. 20, 941–960 (2021). · DOI
  47. Rodrigo-Navarro, A., Sankaran, S., Dalby, M. J., del Campo, A. & Salmeron-Sanchez, M. Engineered living biomaterials. Nat. Rev. Mater. 6, 1175–1190 (2021). · DOI

Metadata

Authors
Xing, J., Zheng, X., Ren, Y., Schuler, M., Ng, D. Y. W., Weil, T., Wegner, S. V., & Synatschke, C. V.
Affiliations
  • Max Planck Institute for Polymer Research (DE)
  • University of Münster (DE)
Corresponding author
  • Wegner, Seraphine V.
  • Synatschke, Christopher V.
Venue
Nature Chemical Biology
Published
2026-07-17
Volume
22
Issue
10
Pages
1676-1684
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W4409955382
Cited by
0
References
1
FWCI
0.00
Type
journal article
Language
en
Open access
Locations
  • Nature Chemical Biology (publishedVersion, cc-by)
  • ChemRxiv (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Fraunhofer and Max Planck cooperation program
  • Deutsche Forschungsgemeinschaft (SFB 1459/2 2025 – 433682494)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
  • Physical Sciences › Chemistry › Organic Chemistry › Supramolecular Chemistry and Complexes
Keywords
intracellular homeostasis, redox homeostasis, energy homeostasis, methionine sulfoxide, methionine sulfoxide reductase, bacterial internalization, photooxidative stress, engineered bacteria
MeSH terms
Escherichia coli, Homeostasis, Methionine, Oxidation-Reduction, Peptides, Photosensitizing Agents, Oxidative Stress, Nanostructures, Nanoparticles, Nanofibers

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