Pioneering research using bacteria brings scientists closer to creating artificial cells with realistic functions

September 15, 2022

(Nanwerk NewsScientists have harnessed the potential of bacteria to help build advanced artificial cells that mimic real-life functions.

The research, led by the University of Bristol and published in temper nature (“Synthesis of living material for protobacterial cells”), is making important advances in the propagation of artificial cells, known as protocells, to more accurately represent the complex structures, structure, and function of living cells. amoeba-shaped germ cell: membrane (red border); core (blue); cytoskeleton (red threads); gap (red circle); ATP production (green). Scale bar, 5 µm. (Photo: Professor Stephen Mann and Dr. Kan Shaw)

Establishing true functions in protocells is a major global challenge that spans multiple fields, from bottom-up synthetic biology and bioengineering to origin of life research. Previous attempts to model protocells using microcapsules failed, so the team of researchers turned to bacteria to build complex synthetic cells using the process of assembling living materials.

Professor Stephen Mann from the University of Bristol’s School of Chemistry, the Max Planck Bristol Center for Minimal Biology together with colleagues Dr Kahn Shaw and Nicholas Martin (currently at Purdue University) and Mei Lee at the Bristol ProtoLife Research Center demonstrated. An approach to construct highly complex primary cells using viscous microdroplets filled with live bacteria as a microscopic construction site.

In the first step, the team exposed the empty droplets to two types of bacteria. One group was spontaneously captured inside the droplets while the other group was trapped on the surface of the droplets.

Subsequently, both types of bacteria were destroyed so that the released cellular components remain trapped inside or on the surface of the droplets to produce membrane-encapsulated protobacterial cells containing thousands of molecules, parts, and biological machinery.

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

After testing the ability of this technique, the team used a series of chemical steps to structurally and morphologically reshape bacterial protocells. The released bacterial DNA was condensed into a nucleolar-like structure, and the interior of the droplet was permeated with a cytoskeleton-like network of protein filaments and membrane-enclosed hydrophilic vacuoles.

As a step towards building an artificial/living cell entity, the researchers implanted live bacteria into primary cells to generate self-sustaining ATP production and long-term activation of glycolysis, gene expression and cytoskeleton assembly. Curiously, the primary structures have adopted an amoeba-like external morphology due to bacterial metabolism in situ and growth to produce a cellular biogenic system with integrated life-like properties.

Corresponding author Professor Stephen Mann said: “Achieving a high degree of regulatory and functional complexity in artificial cells is challenging especially under conditions close to homeostasis. We hope that our current approach to bacterial generation will help increase the complexity of existing protocell models, facilitating the integration of a myriad of biological components and enable the development of active cellular mimetic systems.”

First author Dr Kan Zhou, Research Associate at the University of Bristol, added: “Our approach to synthesizing living materials provides an opportunity for bottom-up construction of symbiotic living/synthetic cell assemblies. For example, using engineered bacteria, it should be possible to fabricate complex units for development in the diagnostic and therapeutic fields. for synthetic biology as well as for biomanufacturing and biotechnology in general.”