Building tiny bacteria-fighters from the bottom up

Faculty, researchers and students at the UC Davis Biomedical Engineering Department’s Tan Lab report they’ve successfully created bacteria-killing artificial cells that operate even in the poorest environments.

Documenting their three years of efforts in a paper published in ACS Applied Materials and Interfaces, team members outline key findings that hold promise in humankind’s age-old battle against harmful – and often even deadly — bacteria.

“We engineered artificial cells from the bottom-up – like Lego blocks — to destroy bacteria,” said team leader Dr. Cheemeng Tan, noting the cells are built from liposomes and purified cellular components: proteins, DNA and metabolites. “We demonstrated that artificial cells can sense, react and interact with bacteria, as well as function as systems that both detect and kill bacteria with little dependence on their environment.”

The team’s artificial cells:

• BEHAVE IN AN EASILY CONTROLLED MANNER – While they behave in many ways like natural cells, the short-lived artificial cells do not divide – they simply mimic essential features of natural cells and efficiently perform specific designed functions.
• WORK IN NUTRIENT-POOR ENVIRONMENTS – Artificial cells previously only had been successful in nutrient-rich environments. However, by optimizing the artificial cells’ membranes, cytosol and genetic circuits, the team made them work in a wide variety of environments with very limited resources such as water, emphasizing their robustness in less-than-ideal or changing conditions. With these improvements, the cells act like aircraft that can fly regardless of weather – sunny or snowy — significantly broadening the overall potential application of artificial cells.
• ATTACK BACTERIA IN RESPONSE TO CHEMICAL SIGNALS – Using common E. coli bacteria for experiments, team members found the artificial cells detected, attacked and destroyed the bacteria by responding to its unique chemical signature.

Tan team members already are working hard on their progress in hopes of eventually tackling harmful or even antibiotic-resistant bacteria, among many other possible live-saving and life-improving uses for their artificial cells.

“We are building on this combination of discoveries to engineer artificial cells for biomedical, biosensing and therapeutic applications,” added main authors Luis Contreras-Llano and Yunfeng Ding. “It’s a new frontier.”

***

“Minimizing Context-Dependency of Gene Networks Using Artificial Cells” by Dr. Cheemeng Tan, Postdoctoral Fellow Yunfeng Ding, Postdoctoral Fellow Eliza Morris, Graduate Student Luis E. Contreras-Llano and Undergraduate Student Michelle Mao appears in ACS Applied Materials and Interfaces: https://pubs.acs.org/doi/full/10.1021/acsami.8b10029. The research was funded by a Society-in-Science: Branco-Weiss Fellowship and an NSF-CHE 1808237-0 grant to Professor Cheemeng Tan, and a UC MEXUS-CONACYT Doctoral Fellowship to Luis E. Contreras-Llano.