Researchers used bacteria to bring synthetic cells a step closer to reality. A team from the University of Bristol, UK, created protocells that can accurately copy complex structures and functions of living cells, according to a study published in the scientific journal Nature.
The creation of protocells that can perform the functions of living cells is a global challenge that includes many different fields, from synthetic biology to bioengineering and research about the origins of life. Previous attempts to make protocells have been largely unsuccessful, but the team from Bristol think bacteria may be the answer.
In this study, Professor Stephen Mann from the University of Bristol and colleagues Drs Can Xu, Nicolas Martin, and Mei Li from the Bristol Centre for Protolife Research showed a viable way to build highly complex protocells using micro-droplets filled with living bacteria as a microscopic building site.
“Achieving high organisational 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 energised cytomimetic systems,” said author Professor Stephen Mann.
First, the team exposed the empty droplet to two types of bacteria: one type within the droplets and the other trapped at the droplet surface. Bacteria were then destroyed, and the cellular components either remained trapped inside or on the surface of the droplet to produce protocells with thousands of biological parts and cellular machinery.
During the study, the team noticed that the protocells were able to produce energy via glycolysis and synthesise RNA and proteins by in vitro gene expression, which shows that the parts inherited from bacteria remain operational.
To continue testing the protocell’s abilities, the researchers used a series of chemical steps to change the protocells structure and morphology. The released bacterial DNA was reorganised into a structure similar to the nucleus, and the droplets were filled with a structure similar to the cytoskeleton using protein filaments.
To build a fully independent living structure, the team added living bacteria to the protocells to produce energy, gene expression, and cytoskeleton assembly. Curiously, the protocells adopted an external morphology similar to an amoeba.
“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,” concluded first author Dr. Can Xu, Research Associate at the University of Bristol.
Xu, C., Martin, N., Li, M. et al. Living material assembly of bacteriogenic protocells.Nature (2022).https://doi.org/10.1038/s41586-022-05223-w