Abstract

Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications.

Highlights

  • In 1665, Hooke observed cellular structure from cork materials and coined the word “cell”

  • This review focuses on artificial cells that are composed of a lipid bilayer, transcriptional/translational machinery and genetic information, with special emphasis on the application of synthetic biology in the construction of artificial cells

  • The phosphatidic acid (PA) synthesis pathway was reconstituted inside liposomes, which generated functional sn-glycerol-3-phosphate acyltransferase (GPAT) and lysophosphatidic acid acyltransferase (LPAAT) for membrane growth (Figure 7a) [19]

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Summary

Introduction

In 1665, Hooke observed cellular structure from cork materials and coined the word “cell”. The definition of artificial cells is broad and includes various types of synthetic cells: protocells for addressing questions about the origin of life [22,23,24,25,32,33]; minimal natural cells that possess only the necessary genes for their basic maintenance [34,35,36,37,38,39]; and artificial cells that are constructed using synthetic membranes and cellular components [27,29,40,41]. We discuss the bridging of these gaps using synthetic biology approaches, focusing on genetic circuits, non-genetic factors, cell communication and self-reproduction The filling of these gaps will eventually enable robust and efficient artificial cells (Figure 1). Division machinery may be implemented to achieve self-replication in artificial cells

Construction of Artificial Cells
Gaps between Artificial and Natural Cells
The Design of Genetic Circuits to Control Functions of Artificial Cells
Communication between Artificial Cells and Their Environment
Replication and Division of Artificial Cells
Conclusions and Future Outlook
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