Living materials with programmable functionalities grown from engineered microbial co-cultures


Biological systems assemble living materials that are autonomously patterned, can self-repair and can sense and respond to their environment. The field of engineered living materials aims to create novel materials with properties similar to those of natural biomaterials using genetically engineered organisms. Here, we describe an approach to fabricating functional bacterial cellulose-based living materials using a stable co-culture of Saccharomyces cerevisiae yeast and bacterial cellulose-producing Komagataeibacter rhaeticus bacteria. Yeast strains can be engineered to secrete enzymes into bacterial cellulose, generating autonomously grown catalytic materials and enabling DNA-encoded modification of bacterial cellulose bulk properties. Alternatively, engineered yeast can be incorporated within the growing cellulose matrix, creating living materials that can sense and respond to chemical and optical stimuli. This symbiotic culture of bacteria and yeast is a flexible platform for the production of bacterial cellulose-based engineered living materials with potential applications in biosensing and biocatalysis.

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Fig. 1: Generating Syn-SCOBY co-cultures with S. cerevisiae and K. rhaeticus.
Fig. 2: Syn-SCOBYs can produce enzyme-functionalized BC materials.
Fig. 3: Modifying BC physical material properties.
Fig. 4: Syn-SCOBY materials can sense and respond.
Fig. 5: Optical patterning of enzymatically functionalized BC materials.

Data availability

All produced data that support the main figures of this study are included in this published article. Data points for the mechanical and rheological tests are provided as Source data files. Additional data are available from the corresponding author upon request.


  1. 1.

    Chen, A. Y., Zhong, C. & Lu, T. K. Engineering living functional materials. ACS Synth. Biol. 4, 8–11 (2015).

    Google Scholar 

  2. 2.

    Nguyen, P. Q. Synthetic biology engineering of biofilms as nanomaterials factories. Biochem. Soc. Trans. 45, 585–597 (2017).

    CAS  Google Scholar 

  3. 3.

    Nguyen, P. Q., Courchesne, N. D., Duraj-Thatte, A., Praveschotinunt, P. & Joshi, N. S. Engineered living materials: prospects and challenges for using biological systems to direct the assembly of smart materials. Adv. Mater. 30, e1704847 (2018).

    Google Scholar 

  4. 4.

    Gilbert, C. & Ellis, T. Biological engineered living materials: growing functional materials with genetically programmable properties. ACS Synth. Biol. 8, 1–15 (2019).

    CAS  Google Scholar 

  5. 5.

    Blanco, L. P., Evans, M. L., Smith, D. R., Badtke, M. P. & Chapman, M. R. Diversity, biogenesis and function of microbial amyloids. Trends Microbiol. 20, 66–73 (2012).

    CAS  Google Scholar 

  6. 6.

    Kalyoncu, E., Ahan, R. E., Olmez, T. T. & Safak Seker, U. O. Genetically encoded conductive protein nanofibers secreted by engineered cells. RSC Adv. 7, 32543–32551 (2017).

    CAS  Google Scholar 

  7. 7.

    Seker, U. O. S., Chen, A. Y., Citorik, R. J. & Lu, T. K. Synthetic biogenesis of bacterial amyloid nanomaterials with tunable inorganic-organic interfaces and electrical conductivity. ACS Synth. Biol. 6, 266–275 (2017).

    CAS  Google Scholar 

  8. 8.

    Dorval Courchesne, N.-M. et al. Biomimetic engineering of conductive curli protein film. Nanotechnology 29, 509501 (2018).

    Google Scholar 

  9. 9.

    Chen, A. Y. et al. Synthesis and patterning of tunable multiscale materials with engineered cells. Nat. Mater. 13, 515–523 (2014).

    CAS  Google Scholar 

  10. 10.

    Moser, F., Voigt, C. A., Tham, E., González, L. M. & Lu, T. K. Light-controlled, high-resolution patterning of living engineered bacteria onto textiles, ceramics, and plastic. Adv. Funct. Mater. 29, 1901788 (2019).

    Google Scholar 

  11. 11.

    Nguyen, P. Q., Botyanszki, Z., Tay, P. K. R. & Joshi, N. S. Programmable biofilm-based materials from engineered curli nanofibres. Nat. Commun. 5, 4945 (2014).

    CAS  Google Scholar 

  12. 12.

    Nussbaumer, M. G. et al. Bootstrapped biocatalysis: Biofilm-derived materials as reversibly functionalizable multienzyme surfaces. ChemCatChem 9, 4328–4333 (2017).

    CAS  Google Scholar 

  13. 13.

    Duraj-Thatte, A. M. et al. Genetically programmable self‐regenerating bacterial hydrogels. Adv. Mater. 31, e1901826 (2019).

    Google Scholar 

  14. 14.

    Dorval Courchesne, N.-M., Duraj-Thatte, A., Tay, P. K. R., Nguyen, P. Q. & Joshi, N. S. Scalable production of genetically engineered nanofibrous macroscopic materials via filtration. ACS Biomater. Sci. Eng. 3, 733–741 (2016).

    Google Scholar 

  15. 15.

    Park, S. J. et al. Phototactic guidance of a tissue-engineered soft-robotic ray. Science 353, 158–162 (2016).

    CAS  Google Scholar 

  16. 16.

    Van Tittelboom, K., De Belie, N., De Muynck, W. & Verstraete, W. Use of bacteria to repair cracks in concrete. Cem. Concr. Res. 40, 157–166 (2010).

    Google Scholar 

  17. 17.

    Wang, J., Van Tittelboom, K., De Belie, N. & Verstraete, W. Use of silica gel or polyurethane immobilized bacteria for self-healing concrete. Constr. Build. Mater. 26, 532–540 (2012).

    Google Scholar 

  18. 18.

    Gerber, L. C., Koehler, F. M., Grass, R. N. & Stark, W. J. Incorporating microorganisms into polymer layers provides bioinspired functional living materials. Proc. Natl Acad. Sci. USA 109, 90–94 (2012).

    CAS  Google Scholar 

  19. 19.

    Gerber, L. C., Koehler, F. M., Grass, R. N. & Stark, W. J. Incorporation of penicillin-producing fungi into living materials to provide chemically active and antibiotic-releasing surfaces. Angew. Chem. Int. Ed. 124, 11455–11458 (2012).

    Google Scholar 

  20. 20.

    Liu, X. et al. Stretchable living materials and devices with hydrogel–elastomer hybrids hosting programmed cells. Proc. Natl Acad. Sci. USA 114, 2200–2205 (2017).

    CAS  Google Scholar 

  21. 21.

    Chawla, P. R., Bajaj, I. B., Survase, S. A. & Singhal, R. S. Microbial cellulose: fermentative production and applications. Food Technol. Biotechnol. 47, 107–124 (2009).

    CAS  Google Scholar 

  22. 22.

    Huang, Y. et al. Recent advances in bacterial cellulose. Cellulose 21, 1–30 (2014).

    Google Scholar 

  23. 23.

    Hsieh, Y. C., Yano, H., Nogi, M. & Eichhorn, S. J. An estimation of the Young’s modulus of bacterial cellulose filaments. Cellulose 15, 507–513 (2008).

    CAS  Google Scholar 

  24. 24.

    Kondo, T., Rytczak, P. & Bielecki, S. in Bacterial Nanocellulose (eds. Gama, M. et al.) 59–71 (Elsevier, 2016).

  25. 25.

    Wang, J., Tavakoli, J. & Tang, Y. Bacterial cellulose production, properties and applications with different culture methods – a review. Carbohydr. Polym. 219, 63–76 (2019).

    CAS  Google Scholar 

  26. 26.

    Ludwicka, K., Jedrzejczak-Krzepkowska, M., Kubiak, K., Kolodziejczyk, M. & Pankiewicz, T. in Bacterial Nanocellulose (eds. Gama, M. et al.) 145–165 (Elsevier, 2016).

  27. 27.

    Yadav, V. et al. Novel in vivo-degradable cellulose-chitin copolymer from metabolically engineered gluconacetobacter xylinus. Appl. Environ. Microbiol. 76, 6257–6265 (2010).

    CAS  Google Scholar 

  28. 28.

    Fang, J., Kawano, S., Tajima, K. & Kondo, T. In vivo curdlan/cellulose bionanocomposite synthesis by genetically modified Gluconacetobacter xylinus. Biomacromolecules 16, 3154–3160 (2015).

    CAS  Google Scholar 

  29. 29.

    Gwon, H. et al. A safe and sustainable bacterial cellulose nanofiber separator for lithium rechargeable batteries. Proc. Natl Acad. Sci. USA 116, 19288–19293 (2019).

    CAS  Google Scholar 

  30. 30.

    Florea, M. et al. Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain. Proc. Natl Acad. Sci. USA 113, E3431–E3440 (2016).

    CAS  Google Scholar 

  31. 31.

    Teh, M. Y. et al. An expanded synthetic biology toolkit for gene expression control in Acetobacteraceae. ACS Synth. Biol. 8, 708–723 (2019).

    CAS  Google Scholar 

  32. 32.

    Jacek, P., Ryngajłło, M. & Bielecki, S. Structural changes of bacterial nanocellulose pellicles induced by genetic modification of Komagataeibacter hansenii ATCC 23769. Appl. Microbiol. Biotechnol. 103, 5339–5353 (2019).

    CAS  Google Scholar 

  33. 33.

    Walker, K. T., Goosens, V. J., Das, A., Graham, A. E. & Ellis, T. Engineered cell-to-cell signalling within growing bacterial cellulose pellicles. Microb. Biotechnol. 12, 611–619 (2018).

    Google Scholar 

  34. 34.

    Jayabalan, R., Malini, K., Sathishkumar, M., Swaminathan, K. & Yun, S. E. Biochemical characteristics of tea fungus produced during kombucha fermentation. Food Sci. Biotechnol. 19, 843–847 (2010).

    CAS  Google Scholar 

  35. 35.

    Lee, M. E., DeLoache, W. C., Cervantes, B. & Dueber, J. E. A highly-characterized yeast toolkit for modular, multi-part assembly. ACS Synth. Biol. 4, 975–986 (2015).

    CAS  Google Scholar 

  36. 36.

    Ong, E., Gilkes, N. R., Miller, R. C., Warren, R. A. & Kilburn, D. G. The cellulose-binding domain (CBD(Cex)) of an exoglucanase from Cellulomonas fimi: production in Escherichia coli and characterization of the polypeptide. Biotechnol. Bioeng. 42, 401–409 (1993).

    CAS  Google Scholar 

  37. 37.

    Antošová, Z., Herkommerová, K., Pichová, I. & Sychrová, H. Efficient secretion of three fungal laccases from Saccharomyces cerevisiae and their potential for decolorization of textile industry effluent – a comparative study. Biotechnol. Prog. 34, 69–80 (2018).

    Google Scholar 

  38. 38.

    Villares, A. et al. Lytic polysaccharide monooxygenases disrupt the cellulose fibers structure. Sci. Rep. 7, 40262 (2017).

    CAS  Google Scholar 

  39. 39.

    Lee, C.-R. et al. Co-fermentation using recombinant Saccharomyces cerevisiae yeast strains hyper-secreting different cellulases for the production of cellulosic bioethanol. Sci. Rep. 7, 4428 (2017).

    Google Scholar 

  40. 40.

    Bhagia, S., Dhir, R., Kumar, R. & Wyman, C. E. Deactivation of cellulase at the air–liquid interface is the main cause of incomplete cellulose conversion at low enzyme loadings. Sci. Rep. 8, 1350 (2018).

    Google Scholar 

  41. 41.

    Yamanaka, S. et al. The structure and mechanical properties of sheets prepared from bacterial cellulose. J. Mater. Sci. 24, 3141–3145 (1989).

    CAS  Google Scholar 

  42. 42.

    Soykeabkaew, N., Sian, C., Gea, S., Nishino, T. & Peijs, T. All-cellulose nanocomposites by surface selective dissolution of bacterial cellulose. Cellulose 16, 435–444 (2009).

    CAS  Google Scholar 

  43. 43.

    Shi, X., Zheng, F., Pan, R., Wang, J. & Ding, S. Engineering and comparative characteristics of double carbohydrate binding modules as a strength additive for papermaking applications. Bioresources 9, 3117–3131. (2014).

    Google Scholar 

  44. 44.

    Butchosa, N., Leijon, F., Bulone, V. & Zhou, Q. Stronger cellulose microfibril network structure through the expression of cellulose-binding modules in plant primary cell walls. Cellulose 26, 3083–3094 (2019).

    CAS  Google Scholar 

  45. 45.

    McIsaac, R. S., Gibney, P. A., Chandran, S. S., Benjamin, K. R. & Botstein, D. Synthetic biology tools for programming gene expression without nutritional perturbations in Saccharomyces cerevisiae. Nucleic Acids Res. 42, e48 (2014).

    CAS  Google Scholar 

  46. 46.

    McIsaac, R. S. et al. Fast-acting and nearly gratuitous induction of gene expression and protein depletion in Saccharomyces cerevisiae. Mol. Biol. Cell 22, 4447–4459 (2011).

    CAS  Google Scholar 

  47. 47.

    Pothoulakis, G. & Ellis, T. Synthetic gene regulation for independent external induction of the Saccharomyces cerevisiae pseudohyphal growth phenotype. Commun. Biol. 1, 7 (2018).

    Google Scholar 

  48. 48.

    Ostrov, N. et al. A modular yeast biosensor for low-cost point-of-care pathogen detection. Sci. Adv. 3, e1603221 (2017).

    Google Scholar 

  49. 49.

    Cardinal-Watkins, C. & Nicell, J. A. Enzyme-catalyzed oxidation of 17β-estradiol using immobilized laccase from trametes versicolor. Enzyme Res. 2011, 725172 (2011).

    Google Scholar 

  50. 50.

    Adeel, M., Song, X., Wang, Y., Francis, D. & Yang, Y. Environmental impact of estrogens on human, animal and plant life: a critical review. Environ. Int. 99, 107–119 (2017).

    CAS  Google Scholar 

  51. 51.

    Avar, P. et al. β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin. Environ. Sci. Pollut. Res. 23, 11630–11638 (2016).

    CAS  Google Scholar 

  52. 52.

    Pathak, G. P., Strickland, D., Vrana, J. D. & Tucker, C. L. Benchmarking of optical dimerizer systems. ACS Synth. Biol. 3, 832–838 (2014).

    CAS  Google Scholar 

  53. 53.

    Jarque, S., Bittner, M., Blaha, L. & Hilscherova, K. Yeast biosensors for detection of environmental pollutants: current state and limitations. Trends Biotechnol. 34, 408–419 (2016).

    CAS  Google Scholar 

  54. 54.

    Adeniran, A., Stainbrook, S., Bostick, J. & Tyo, K. Detection of a peptide biomarker by engineered yeast receptors. ACS Synth. Biol. 7, 696–705 (2018).

    CAS  Google Scholar 

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We thank G. Pothoulakis, C. Bricio-Garberi, B. E. Wolfe and E. Landis for advice and discussions, J. van der Hilst for contributions to co-culture methods and B. An for assisting with photo taking. Work at Imperial College London was funded by UK Engineering and Physical Sciences Research Council (EPSRC) awards EP/M002306/1 and EP/N026489/1 and an Imperial College London President’s Scholarship to C.G. W.O. was supported by a research fellowship (OT 577/1-1) from the German Research Foundation (DFG). Work at MIT was funded by Army Research Office award W911NF-11-1-0281 and Institute for Soldier Nanotechnologies award W911NF-13-D-0001, T.O. 4. T.C.T. was supported by the MIT J-WAFS Fellowship. Work across both institutions was funded by the MIT-MISTI MIT-Imperial College London Seed Fund.

Author information




C.G., T.-C.T. and T.E. conceived and designed the experiments. C.G., T.-C.T. and W.O. performed the Syn-SCOBY co-culture characterization experiments. C.G. performed the BC functionalization and biosensor experiments. T.-C.T. performed yeast incorporation, BC material property modification and optical-patterning experiments. B.A.D. generated yeast strains for optical patterning. W.M.S. generated yeast biosensor strains and genetic tools. G.L.S. performed the eSEM experiments. T.K.L. and T.E. supervised the project and C.G., T.-C.T., W.O. and T.E. wrote the manuscript.

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Correspondence to Timothy K. Lu or Tom Ellis.

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C.G., T.-C.T., W.O., T.K.L. and T.E. are co-inventors on patent applications (International Patent Application no. PCT/US2020/047330) filed by MIT and Imperial College London relating to all the work covered in this article.

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Gilbert, C., Tang, TC., Ott, W. et al. Living materials with programmable functionalities grown from engineered microbial co-cultures. Nat. Mater. (2021).

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