• Kayla Hui

Synthetic Cells

Throughout biology, there are several characteristics taught that differentiate living from non-living matter. Life is organized, uses energy, maintains internal consistency, grows and develops to reproduce, and evolves. These are the main few but there are other interpretations as to what defines life. However innovations, such as synthetic cells, are beginning to blur the line in what distinguishes life from non-living matter. Along with the question of what factors create “life”.

Synthetic cells, also known as artificial cells, are artificial structures where biological active components, such as proteins, genes, enzymes, or other cellular structures, are within an artificial membrane. This artificial membrane also hopes to allow small molecules to rapidly diffuse across it, similar to the semi-permeable membrane of the human body. With these characteristics, it is hoped that they can be suitable substitutes for natural cells. Artificial cells have a variety of applications in many fields ranging from medicine to the environment, including improving theories on the origin of life.

Artificial cells are predicted to be more well-controlled and more robust than natural cells. For this reason shows promise in a variety of fields such as cell engineering, biotechnology, medicine, drug delivery, biosensors, pharmaceuticals, bioremediation, and many more. However, even current unicellular organisms are entirely extremely complex, and many issues with the creation of artificial cells have arisen.

Current synthetic cells can be defined in several ways. There are two main categories of artificial cells: typical and non-typical artificial cells. The typical artificial cells contain cell-like structures and exhibit essential aspects of living matter. The main purpose of typical artificial cells is to construct synthetic cells which could be considered alive based on their characteristics. As stated, the definition for alive is difficult to define, but the main consensus is the traits that were stated earlier. There have been two approaches for creating a typical artificial cell: the top-bottom approach and the bottom-top approach.

The top-bottom approach promotes starting from a living organism then “stripping down” the genome of the organism to the lowest number of genes required to maintain cellular life, or replacing the genome with an artificial version. This focuses on building minimal cells, theoretical cells that have the minimum number of genes needed to provide essential life functions, by simplifying the genome of the living cell. The bottom-top approach promotes starting from scratch and assembling biological or non-biological molecules to construct a “living” cell. Three essential components are needed for the construction of “living” synthetic cells: information-carrying molecules, cell membranes, and metabolism systems.

Non-typical artificial cells, or ‘cell mimics’, are engineered materials that mimic one or more features of the biological cells but do not have restrictions in certain structures. These can imitate some characteristics of cells such as surface characteristics, shape, function, or even the morphology of the cell. Surface mimics imitate the functions performed by the membrane of cells such as cell to cell communication. The shape of a cell is crucial for its functions. For example, red blood cells have a biconcave discoid shape which allows them to go through narrow capillaries. Morphology, the form of living organisms and the relationships between their structures, are also important for their functions. In 2012 a biomineralization method that could capture the morphology of mammalian cells was developed. Function mimics are non-typical artificial cells that are constructed to mimic cell functions directly.

Due to their multitude of capabilities synthetic cells have been a long-awaited innovation, with researchers trying to create them for over 20 years. Recently creating synthetic cells has become easier, due to advances in microfluidic technologies, which allow scientists to track movements of cellular components. Researchers have already created rudimentary cell-like structures along with basic versions of metabolism. However, it is exceedingly difficult to bring the different components together.

In 2016 researchers at the Craig Venter Institute created a synthetic, minimal cell with a genome that contained only 473 key genes. As of 2021, another project, a collaboration between the J. Craig Venter Institute, the National Institute of Standards and Technology, and the Massachusetts Institute of Technology Center for Bits and Atoms has identified seven genes that can be added to stabilize cell division. The original minimal cell often behaved strangely when dividing and developing, these seven genes have been shown to stabilize cell division. For further projects, MIT author, Jame Pelletier, hopes to “know the function of every gene so we can develop a complete model of how a cell works”.

In September 2017 Building a Synthetic Cell (BaSYC) was formed from research from seventeen different laboratories. BaSYC hopes to construct a system for the growth and division of cells. This project is generously funded by a 21.3 million dollar Dutch Gravitation grant.

BaSYC has had numerous publications that are all in hopes to create an autonomous, self-reproducing cell. BaSYC is currently using the bottom-up approach which is combining various components/systems to give rise to a more complex creation. For this reason, BaSYC has seven work packages (WPs), each dedicated to different characteristics of the cell, which are also the characteristics of living matter. This includes cell fueling which is to engineer a minimal metabolism that can supply the vesicle with the necessary energy to maintain homeostasis, operate replication, and many other necessary things. Another work package is cell division to allow for the constriction and fission of the vesicle. There are also other equally important and fascinating work packages.

Overall synthetic cells are a promising innovation that has many more aspects to be uncovered. Due to their complexity and variations, it is unlikely that a synthetic cell will be functional soon, but it is a project to look forward to in the future. Synthetic cells would provide a solution for a wide variety of problems and it should be interesting to watch the development of synthetic cells.