4.8 Article

Hydrogel-based biocontainment of bacteria for continuous sensing and computation

Journal

NATURE CHEMICAL BIOLOGY
Volume 17, Issue 6, Pages 724-731

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41589-021-00779-6

Keywords

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Funding

  1. National Institutes of Health (NIH) New Innovator Award [1DP2OD008435]
  2. NIH National Centers for Systems Biology [1P50GM098792]
  3. US Office of Naval Research [N00014-13-1-0424]
  4. Defense Advanced Research Projects Agency [HR0011-15-C-0091]
  5. NIH [1R01HL153857-01]
  6. National Science Foundation [EFMA-1935291]
  7. US Army Research Office through the Institute for Soldier Nanotechnologies at MIT [W911NF-13-D-0001]
  8. Institute for Diabetes, Obesity, and Metabolism
  9. Penn Mental Health AIDS Research Center of the University of Pennsylvania
  10. National Institute of General Medical Sciences of the NIH [R35GM138201]
  11. Defense Threat Reduction Agency [HDTRA11810041, HDTRA1-21-1-0014]
  12. Abdul Latif Jameel Water and Food Systems Laboratory (J-WAFS) Graduate Student Fellowship
  13. U.S. Department of Defense (DOD) [HDTRA11810041] Funding Source: U.S. Department of Defense (DOD)

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A hydrogel-based encapsulation system, known as DEPCOS, has been developed to provide deployable physical containment for genetically modified microorganisms, preventing their escape and protecting them against environmental insults. It also allows for controlled lifespan and easy retrieval of bacteria, showcasing versatility in executing useful functions such as cell-cell communication and heavy metal sensing.
Genetically modified microorganisms (GMMs) can enable a wide range of important applications including environmental sensing and responsive engineered living materials. However, containment of GMMs to prevent environmental escape and satisfy regulatory requirements is a bottleneck for real-world use. While current biochemical strategies restrict unwanted growth of GMMs in the environment, there is a need for deployable physical containment technologies to achieve redundant, multi-layered and robust containment. We developed a hydrogel-based encapsulation system that incorporates a biocompatible multilayer tough shell and an alginate-based core. This deployable physical containment strategy (DEPCOS) allows no detectable GMM escape, bacteria to be protected against environmental insults including antibiotics and low pH, controllable lifespan and easy retrieval of genomically recoded bacteria. To highlight the versatility of DEPCOS, we demonstrated that robustly encapsulated cells can execute useful functions, including performing cell-cell communication with other encapsulated bacteria and sensing heavy metals in water samples from the Charles River. A dual-layer encapsulation approach provides physical containment of genetically modified bacteria (especially when combined with chemical containment) while also protecting them from environmental stressors and maintaining their sensing functions.

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