Interfacing Living and Synthetic Cells as an Emerging Frontier in Synthetic Biology

Abstract

The construction of artificial cells from inanimate molecular building blocks is one of the grand challenges of our time. In addition to being used as simplified cell models to decipher the rules of life, artificial cells have the potential to be designed as micromachines deployed in a host of clinical and industrial applications. The attractions of engineering artificial cells from scratch, as opposed to re-engineering living biological cells, are varied. However, it is clear that artificial cells cannot currently match the power and behavioural sophistication of their biological counterparts. Given this, many in the synthetic biology community have started to ask: is it possible to interface biological and artificial cells together to create hybrid living/synthetic systems that leverage the advantages of both? This article will discuss the motivation behind this cellular bionics approach, in which the boundaries between living and non-living matter are blurred by bridging top-down and bottom-up synthetic biology. It details the state of play of this nascent field and introduces three generalised hybridisation modes that have emerged.

Keywords: artificial cells; biotechnology; cellular bionics; molecular bioengineering; synthetic biology.

Figure 1

Cellular bionics. Hybrid cellular bionic systems can be constructed by fusing living and non‐living modules together. Living modules can be cells (prokaryotic or eukaryotic) or organelles (e.g. mitochondria and chloroplasts). Non‐living modules can consist of artificial cell‐like compartments that are composed of biological and synthetic molecular components (e.g. enzymes, membrane proteins, DNA, and nanoparticles).

Figure 2

Schematic of the main cellular bionic hybridisation modes in which living and synthetic cells are chemically or physically interfaced with each other.

Figure 3

Population hybridisation. A) Schematic of artificial cells translating a chemical signal (theophylline) into a signal (IPTG) which E. coli can sense and respond to through GFP expression. FACS results showing a shift in fluorescence of the E. coli population in the presence of artificial cells plus theophylline are shown below. Image modified with permission from Ref. . B) Schematic of an artificial cell mediating communication between V. fischeri and engineered E. coli through the sensing and releasing of different quorum‐sensing molecules. FACS results showing successful communication through GFP expression in E. coli are shown below. Image modified with permission from Ref. .

Figure 4

Embedded hybridisation. A–C) Examples of living cells encapsulated in synthetic ones. A) Engineered eukaryotic cells encapsulated in an artificial cell containing a synthetic metabolism. Coupling the living and synthetic cells in this way resulted in an enzymatic cascade leading to the production of a fluorescent molecule (resorufin) within the hybrid bioreactor. Figure modified with permission from Ref. . B) Microscopy images showing chloroplasts (red) encapsulated in coacervates (green). Chloroplasts retained their light‐induced electron transport capabilities, as demonstrated by the reduction of a Hill reagent (DPIP), depicted in the schematic. Figure modified with permission from Ref. . C) Schematic of a chromatophore organelle extracted from a photosynthesising organism and inserted in a synthetic cell. Upon light irradiation, this led to the production of ATP, which powered the translation apparatus to produce mRNA. Figure modified with permission from Ref. . Copyright 2020, the authors. D) An example of a synthetic cell encapsulated in a living one. The synthetic cells performed an organelle‐like function by degrading H₂O₂, thus shielding the cell from the detrimental effects of this molecule. Image modified with permission from Ref. .