Artificial Cells With Lifelike Functionality – New Breakthrough Brings Scientists One Step Closer

The study uses bacteria to bring scientists closer to building these artificial lifelike cells.

Researchers have used bacteria to help develop advanced synthetic cells that imitate the real-life functionality of cells.

The study, conducted by the University of Bristol and published in the journal Nature, advances the development of synthetic cells, or protocells, to more precisely replicate the complex composition, structure, and function of living cells.

Establishing true-to-life functionality in protocells is a global great challenge involving several fields, from the origin of life research to bottom-up synthetic biology and bioengineering. Due to previous failures in modeling protocells using microcapsules, the research team turned to bacteria to construct sophisticated synthetic cells utilizing a living material assembly process.

Bacteria as Building Blocks for Protocell Assembly

Professor Stephen Mann from the School of Chemistry at the University of Bristol and the Max Planck Bristol Centre for Minimal Biology, and colleagues Drs. Can Xu, Nicolas Martin (now 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 initially exposed the empty droplets to two different types of bacteria. One population was captured spontaneously inside the droplets, while the other was confined at the droplet surface.

Then, both types of bacteria were destroyed so that the released cellular components remained trapped inside or on the surface of the droplets to produce membrane-coated bacteriogenic protocells containing thousands of biological molecules, parts, and machinery.

Achieving Cellular Functions in Synthetic Cells

The researchers discovered that the protocells were able to produce energy-rich molecules (ATP) via glycolysis and synthesize RNA and proteins by in vitro gene expression, indicating that the inherited bacterial components remained active in the synthetic cells.

Further testing the capacity of this technique, the team employed a series of chemical steps to remodel the bacteriogenic protocells structurally and morphologically. The released bacterial DNA was condensed into a single nucleus-like structure, and the droplet interior infiltrated with a cytoskeletal-like network of protein filaments and membrane-bounded water vacuoles.

As a step towards the construction of a synthetic/living cell entity, the researchers implanted living bacteria into the protocells to generate self-sustainable ATP production and long-term energization for glycolysis, gene expression, and cytoskeletal assembly. Curiously, the protoliving constructs adopted an amoeba-like external morphology due to on-site bacterial metabolism and growth to produce a cellular bionic system with integrated life-like properties.

Corresponding author Professor Stephen Mann said: “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.”

Future Applications in Synthetic Biology and Biotechnology

First author Dr. Can Xu, a Research Associate at the University of Bristol, added: “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.”

Reference: “Living material assembly of bacteriogenic protocells” by Can Xu, Nicolas Martin, Mei Li, and Stephen Mann, 14 September 2022, Nature.
DOI: 10.1038/s41586-022-05223-w

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