Synthetic Cell

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A synthetic cell is an engineered particle that mimics one or many functions of a biological cell. The concept of artificial cells was first proposed by Dr. Thomas Ming Swi Chang in 1957. The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. These have attracted much attention as substitutes for natural cells. These artificial cells can have applications in many fields from medicine to environment, and may be useful in constructing the theory of the origin of life. However, even the simplest unicellular organisms are extremely complex and synthesis of living artificial cells from inanimate components seems very daunting. Nevertheless, recent progress in the formulation of artificial cells suggests that the construction of living life is now not an unrealistic goal.

Modern cell biology is not satisfied by just investigating the structure, functions and working principles of cells. The research has expanded into many new areas such as the origin of life, cell engineering, biotechnology, bio-factories, medicine, drug delivery, pharmaceuticals, biosensors, and bioremediation. However, along with the rapid development of cell biology, many issues have arisen mainly because of the inherent complexity of biological cells as well as the frangibility, that is to say, easy loss of activity or death in vitro. To overcome these issues while still mimicking biological cells, artificial cells are built which are expected to be more easily controlled and are more robust than natural cells. They can also be used as biomimetic systems to study and understand properties of biological cells, to investigate the dynamics of cells with minimal interference from cellular complexity, and to explore new possible applications in place of biological cells.

Artificial cells can be classified into two main categories based upon their intrinsic characteristics – typical and non-typical. The typical ones are artificial cells in ‘full-sense’. Strictly speaking, the typical artificial cells should have cell-like structures and exhibit at least some of the key characteristics of living biological cells, such as to evolve, to self-reproduce and to metabolize. The non-typical artificial cells, on the other hand, are engineered materials that mimic one or more features of biological cells and most importantly, have no restrictions in structure. The more precise definition of these materials would be ‘cell mimics’ that mimic some functions, surface characteristics, shapes, and even morphology of biological cells.

Typical Artificial Cells:

Typical artificial cells should ideally have similar structures and essential properties of living cells. The ultimate goal is to construct artificial cells that can be considered as ‘alive’.  even the simplest known organisms are very complex, making the efforts to synthesize ‘living’ artificial cells arduous and very challenging. Biological cells possess three main components for performing the essential functions of life:

1. A stable, semi-permeable membrane that encloses cell constituents protecting them from being damaged by the external environment while allowing selective material and energy exchanges.
2. Biomacromolecules (DNA or RNA) that carry the genetic information, control the dynamics of the cell, and endow it with the capability of evolution.
3. A series of metabolic pathways used for providing energy to cells, to make them self-maintain and self-renew, as well as self-process information.

It is highly desirable that artificial cells possess all three features of biological cells. Although an artificial cell that possesses all basic properties of a living cell has not been created so far, recent advancements indicate that it is now a realistic goal.

Credit: BioTechSpace | Image: Google

Up till now, two main fundamental approaches have been considered for the construction of an artificial cell: A top-down approach and a bottom-up approach. The top-down approach starts from a living organism, stripping down the genome to the lowest number of genes that are required to maintain the essential properties of the cellular life, or totally replacing the genome with a synthetic one. In contrast, the bottom-up approach starts from scratch. It constructs a ‘living’ artificial cell by assembling biological and/or non-biological molecules. These two approaches are very different but complementary to each other, fabricating a broad range of artificial cells from a simple protocell to an engineered living life.

Non-Typical Artificial Cells:

The non-typical artificial cells are engineered materials that simulate one or more features of biological cells and, most importantly, no restrictions on structures. They are more precisely called ‘cell mimics’ that imitate some surface characteristics, shapes, functions, or even morphology of biological cells. Based on their function, they are:

1. Surface mimics:- A variety of receptors, antigens, and ligands present on the surface membrane of cells perform diverse functions such as cell-cell communication. Mimicking surface characteristics, in a sense, provides an efficient way to emulate some or all of the functions of template cells. Two main methods for cell surface mimicking have been described: one is to incorporate some of the functional membrane groups into the designed particles, and the other is to coat the particles with intact cell membranes directly with or without further modifications.
2. Shape Mimics:- In addition to surface characteristics, shape and mechanical properties are also crucial for cellular functions. Particles with unique physical properties that are similar to cells have been fabricated and shown to be capable of replicating some of the functions of cells. For eg: Because of the biconcave discoidal shape, RBCs have high flexibility and can squeeze through narrow capillaries with diameters smaller than the size of the cells allowing them to circulate efficiently in vivo. So, by using this property we can synthesize cells to pass through cells and capillaries.
3. Morphology Mimics:- For many mammalian cells and organisms, their unique morphologies are critical for their functions. For example, the ultrafine morphology enables immunocytes to capture the cellular debris, abnormal cells, and foreign substances efficiently. This property can be used to eliminate cancer-cells.
4. Function Mimics:- Besides the composition and morphology mimicking, smart systems can also be constructed to mimic cell functions directly. Cell mimic particles, incorporating some beneficial traits of nature cells, have demonstrated promising advantages over traditional particles, especially in the field of biomedicine. Nevertheless, these cell mimic particles represent an advanced bioengineering approach, which incorporates the characteristics of natural cells into non-living materials with very promising and broad biological applications potential.

Synthetic cell technology can be a boon to various fields of science and technology and has the potential to revolutionize the lives of all creatures on Earth. But the consequences of this technology are assumed to be unknown. Moreover it is also being subjected to various Ethics and controversy. Recently Protocell research has created controversy and opposing opinions, including critics of the vague definition of "artificial life". The creation of a basic unit of life is the most pressing ethical concern, although the most widespread worry about protocells is their potential threat to human health and the environment through uncontrolled replication.

REFERENCES:-  

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222523/#:~:text=Research%20on%20these%20synthetic%20cells,iv
• https://en.wikipedia.org/wiki/Artificial_cell#Synthetic_cells

IMAGE SOURCES:-

• https://biotechscope.com/genetically-minimal-synthetic-cells-reveal-new-essential-cell-division-genes/

Written By-

Bhrijesh Mishra and Mrunal Nanda