NanoResCon2023: Researchers have made great strides in utilising bacteria to create artificial cells that function like real cells.

 Researchers have used bacteria to create sophisticated synthetic cells that imitate the activity of genuine cells.

The study, led by the University of Bristol and published today in Nature, advances the use of artificial cells, or protocells, to more faithfully mimic the intricate makeup, structure, and function of living cells.

Establishing true-to-life functioning in protocells is an international great challenge involving several disciplines, from beginning of life research to bottom-up synthetic biology and bioengineering. Due to previous failures in modelling protocells using microcapsules, the study team turned to bacteria to construct sophisticated synthetic cells utilising a living material assembly method.

Professor Stephen Mann from the School of Chemistry at the University of Bristol, the Max Planck Bristol Centre for Minimal Biology, and colleagues Drs. Can Xu, Nicolas Martin (currently at the University of Bordeaux), and Mei Li from the Bristol Centre for Protolife Research have demonstrated a method for building highly complex protocells using viscous micro-droplets filled with living bacteria as a microscopic building site.

The group first exposed the empty droplets to two different bacterial species. While the other population was imprisoned at the droplet surface, one population spontaneously became stuck inside the droplets.

The liberated cellular components were then retained inside or on the surface of the droplets by the destruction of both types of bacteria, resulting in membrane-coated bacteriogenic protocells that contained hundreds of biological molecules, parts, and machinery.

The fact that the protocells could generate RNA and proteins by in vitro gene expression as well as energy-rich molecules (ATP) via glycolysis suggested that the hereditary bacterial components persisted in the synthetic cells.

The scientists used a number of chemical processes to physically and morphologically alter the bacteriogenic protocells in order to test the technique's effectiveness further. The interior of the droplet was filled with a cytoskeletal-like network of protein filaments and membrane-bound water vacuoles, and the liberated bacterial DNA was compressed into a single structure resembling a nucleus.

The researchers inserted living bacteria into the protocells to produce self-sustaining ATP synthesis and long-term energization for glycolysis, gene expression, and cytoskeletal assembly as a first step toward creating a synthetic/living cell entity. Curiously, the protoliving constructions developed an exterior appearance resembling an amoeba as a result of local bacterial growth and metabolism, creating a cellular bionic system with integrated life-like features.

Professor Stephen Mann, the correspondent author, said: "High organisational and functional complexity is challenging to achieve in synthetic cells, especially when close to equilibrium conditions exist. Hopefully, our new bacteriogenic strategy will contribute to the complexity of protocell models now in use, make it easier to integrate a wide range of biological elements, and enable the creation of energetic cytomimetic systems."

Research Associate at the University of Bristol and the study's first author, Dr. Can Xu, added: "Our living-material assembly method offers the chance to build symbiotic living/synthetic cell structures from the bottom up. For instance, it should be able to create sophisticated modules utilising modified bacteria for development in synthetic biology's diagnostic and therapeutic fields as well as in biomanufacturing and biotechnology in general."

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From the University of Bristol, these materials. There may be length and style edits to the content.