In 1957, Dr. Thomas Chang was the first one who proposed the concept of artificial cells. The typical artificial cells are those with cell-like structures and have at least some of the key features of living biological cells, such as self-reproduction, metabolism, and evolution.
They have engineered particles that mimic one or more functions of a biological cell. The main purpose of artificial cells is to investigate characters of biological cells, analyzing the cell dynamics, identifying their potential applications instead of biological cells.
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There are several applications of artificial cells in pharmaceutical, medical, biological, and environmental studies, and they may be helpful in the explanation of the theory of the origin of life.
There are two substantial methods used for the production of artificial cells: a top-down approach and a bottom-up approach.
Top-down approach
It is based on stripping down the genome of living organisms, to keep the lowest number of genes that are needed for the basic features of the cellular life or only to survive.
Venter and colleagues found that the pathogenic bacterium Mycoplasma genitalium, which is among the smallest free-living organisms known, has only 517 genes. This small genome inspired researchers to begin developing minimal cells.
When scientists knocked down non-essential genes, they found that nearly 256-350 genes were needed to keep the cellular life. Further work done by Gil and colleagues revealed that this number of genes needed to maintain basic features of the cellular life can be lowered to 206 genes.
Yet, there are some genes among these 206 genes that can still be removed such as those required for the production of nucleotides and amino acids, bringing the gene number down to nearly 150. However, the meaning of minimal cells is also correlated to the environment type they are in as the survival of these minimal cells demands that the corresponding compounds are obtainable in the environment and can easily enter the cells.
The process of knocking out genes one at a time is burdensome and inefficient. Replacing the original genes of the biological cells with synthetic ones is considered to be a more modern and tricky method in a top-down approach.
Some studies showed promising results in the formation of some primary organisms such as bacteria and viruses. Cello and colleagues created an artificial infectious poliovirus by de novo synthesis of cDNA poliovirus genome from basic chemical building blocks, forming poliovirus with pathological and physiological features comparable to those of the natural poliovirus.
Although viruses are not considered to be living organisms, this study showed the potential to synthesize more complex living organisms without the need to have a genetic template, just by chemical and/or biochemical processes.
In 2010, Gibson and colleagues designed genome sequences (named ‘M. mycoides JCVI-syn1.0’) based on computer study. Although the designed genomes were a little dissimilar from the original genome, the new cells had anticipated phenotypic characters of M. mycoides and could replicate by themselves.
This is very promising, but there are still many concerns and issues to say that we are near to create complex or eukaryotic organisms.
For example, the genome of eukaryotes is very complex and it is hard to create such a complex genome. Although this is a great advance in genome engineering, it is very challenging to obtain an error-free genome.
Bottom-up approach
The bottom-up approach is based on assembling a stack of non-biotic components to create a cell instead of starting from existing living organisms as seen in the top-down approach. Therefore, the bottom-up strategy is more challenging than the top-down approach.
The bottom-up method can fix some of the flaws seen in the top-down approach. For example, the top-down approach is cumbersome and may have some undesirable and unexpected results and untoward biological outcomes.
The systems developed from the bottom-up method, having only minimal constituents required to make the desired functions, are easier and more manageable and can, therefore, overcome the shortcomings of the top-down approach.
For the construction of artificial cells using a bottom-up method, three basic items including information-carrying molecules, cell membranes, and metabolism systems are needed.
Information-carrying molecules (RNA or DNA) determine the type and function of the cell. The cell membrane is considered to be the habitat for cellular components, mediator for external communication, a transporter for many materials, and a site for modulating various cellular processes such as adhesion and migration. Finally, Metabolism provides energy for cells to grow, divide, and transfer information, along with many other vital processes.
The basic biological units in the artificial cell design process are genes. Advances in cell biotechnology allowed scientists to synthesize genomes with several genes in the laboratory, with the help of computer-aided programs.
Following rational assembly and encapsulation inside a vesicle, these custom-made DNA program units could be utilized as software to make the role and function of the artificial cells. Promoters, ribosomes, low molecular weight substances, several enzymes, and various transcription factors are also required.
Artificial cells can be produced by a bottom-up approach which begins from scratch by the assembly of the non-biotic components, or top-down method, in which the non-essential genes are removed from organisms or superseded by synthetic ones.
Sources
- Cello, J., Paul, A.V. and Wimmer, E., 2002. Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. science, 297(5583), pp.1016-1018.
- Fraser, C.M., Gocayne, J.D., White, O., Adams, M.D., Clayton, R.A., Fleischmann, R.D., Bult, C.J., Kerlavage, A.R., Sutton, G., Kelley, J.M. and Fritchman, J.L., 1995. The minimal gene complement of Mycoplasma genitalium. Science, 270(5235), pp.397-404.
- Gibson, D.G., Glass, J.I., Lartigue, C., Noskov, V.N., Chuang, R.Y., Algire, M.A., Benders, G.A., Montague, M.G., Ma, L., Moodie, M.M. and Merryman, C., 2010. Creation of a bacterial cell controlled by a chemically synthesized genome. science, 329(5987), pp.52-56.
- Gil, R., Silva, F.J., Peretó, J. and Moya, A., 2004. Determination of the core of a minimal bacterial gene set. Microbiol. Mol. Biol. Rev., 68(3), pp.518-537.
- Noireaux, V., Maeda, Y.T. and Libchaber, A., 2011. Development of an artificial cell, from self-organization to computation and self-reproduction. Proceedings of the National Academy of Sciences, 108(9), pp.3473-3480.
- Noireaux, V., Maeda, Y.T. and Libchaber, A., 2011. Development of an artificial cell, from self-organization to computation and self-reproduction. Proceedings of the National Academy of Sciences, 108(9), pp.3473-3480.
- Rasmussen, S., Chen, L., Nilsson, M. and Abe, S., 2003. Bridging nonliving and living matter. Artificial life, 9(3), pp.269-316.
- Xu, C., Hu, S. and Chen, X., 2016. Artificial cells: from basic science to applications. Materials Today, 19(9), pp.516-532.
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