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 modeling protocells using microcapsules, the study team turned to bacteria to construct sophisticated synthetic cells utilizing 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, colleagues Drs Can Xu, Nicolas Martin (currently at the University of Bordeaux), and Mei Li from the Bristol Centre for Protolife Research were included in this study.
They have proved a method for creating massively complicated 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 several chemical processes to physically and morphologically alter the bacteriogenic protocells 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. Interestingly, the 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.
Achieving high organizational and functional complexity in synthetic cells is difficult, especially under close-to-equilibrium conditions. Hopefully, our current bacteriogenic approach will help to increase the complexity of current protocell models, facilitate the integration of myriad biological components and enable the development of energized cytomimetic systems.”
Stephen Mann, Study Corresponding Author and Professor, University Of Bristol
First author Dr Can Xu, Research Associate at the University of Bristol, said, “Our living-material assembly approach provides an opportunity for the bottom-up construction of symbiotic living/synthetic cell constructs.”
“For example, using engineered bacteria it should be possible to fabricate complex modules for development in diagnostic and therapeutic areas of synthetic biology as well as in biomanufacturing and biotechnology in general.”
Xu, C., et al. (2022) Living material assembly of bacteriogenic protocells. Nature. doi.org/10.1038/s41586-022-05223-w.