Scientists have harnessed the potential of bacteria to help build advanced synthetic cells that mimic real-life functionality.
The research, led by the University of Bristol and published today in Natureis making significant progress in deploying synthetic cells, called protocells, to more accurately represent the complex compositions, structure, and function of living cells.
Establishing realistic functionalities in protocells is a great global challenge spanning several areas, ranging from bottom-up synthetic biology and bioengineering to research on the origin of life. Previous attempts to model protocells using microcapsules failed, so the research team turned to bacteria to build complex synthetic cells using a process of assembling living materials.
Professor Stephen Mann from the School of Chemistry at the University of Bristol and the Max Planck Bristol Center for Minimal Biology with his colleagues Doctors Can Xu, Nicolas Martin (currently at the University of Bordeaux) and Mei Li from the Bristol Center for Protolife Research demonstrated an approach to building highly complex protocells using viscous micro-droplets filled with live bacteria as a microscopic building site.
First, the team exposed the empty droplets to two types of bacteria. One population was captured spontaneously in the droplets while the other was trapped on the surface of the droplets.
Then both types of bacteria were destroyed so that the cellular components released remained trapped inside or on the surface of the droplets to produce bacteriogenic protocells covered with a membrane containing thousands of molecules, parts and biological machinery. .
Researchers found that protocells were able to produce energy-rich molecules (ATP) via glycolysis and synthesize RNA and proteins through gene expression in vitro, indicating that inherited bacterial components remained active in synthetic cells. .
Further testing the ability of this technique, the team used a series of chemical steps to structurally and morphologically reshape the bacteriogenic protocells. The released bacterial DNA was condensed into a single nucleus-like structure and the interior of the droplets infiltrated with a cytoskeleton-like network of membrane-bound protein filaments and water vacuoles.
As a step towards constructing a synthetic/living cellular entity, researchers implanted live bacteria into the protocells to generate self-sustaining ATP production and long-term potency for glycolysis, gene expression, and assembly of the cytoskeleton. Interestingly, the protoliving constructs adopted an amoeba-like external morphology due to in-place bacterial metabolism and growth to produce a cellular bionic system with lifelike properties built-in.
Corresponding author Professor Stephen Mann said: “Achieving high organizational and functional complexity in synthetic cells is challenging, especially under near-equilibrium conditions. Hopefully, our current bacteriogenic approach will help increase the complexity of current protocell models, facilitate the integration of myriad biological components, and enable the development of energized cytomimetic systems. »
First author Dr Can Xu, a research associate at the University of Bristol, added: “Our approach to assembling living materials 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 the diagnostic and therapeutic areas of synthetic biology as well as in biomanufacturing and biotechnology in general. »