Engineering Cyborg Bacteria Through Intracellular Hydrogelation

Abstract

Natural and artificial cells are two common chassis in synthetic biology. Natural cells can perform complex tasks through synthetic genetic constructs, but their autonomous replication often causes safety concerns for biomedical applications. In contrast, artificial cells based on nonreplicating materials, albeit possessing reduced biochemical complexity, provide more defined and controllable functions. Here, for the first time, the authors create hybrid material‐cell entities termed Cyborg Cells. To create Cyborg Cells, a synthetic polymer network is assembled inside each bacterium, rendering them incapable of dividing. Cyborg Cells preserve essential functions, including cellular metabolism, motility, protein synthesis, and compatibility with genetic circuits. Cyborg Cells also acquire new abilities to resist stressors that otherwise kill natural cells. Finally, the authors demonstrate the therapeutic potential by showing invasion into cancer cells. This work establishes a new paradigm in cellular bioengineering by exploiting a combination of intracellular man‐made polymers and their interaction with the protein networks of living cells.

Abstract

Synthetic biology has made major strides toward creating programmable bio‐micromachines. Despite these efforts, current living synthetic cells are created primarily using genetic approaches, and they autonomously divide. Here, the authors show how assembling a man‐made polymer matrix inside bacteria creates semi‐living entities termed Cyborg Cells. The Cyborg Cells are programmable, do not divide, preserve essential cellular activities, and gain nonnative abilities.