Synthetic cell

The terms synthetic cells, artificial cells or protocells are used to for chemical or biochemical systems based a set of reacting molecules that are enclosed in compartments that mimic cell structure and behavior. The three terms are sometimes used interchangeably and other times they have their own nuanced meanings.

Synthetic cell (SCs) often use lipid vesicles called liposomes to entrap biomolecules such as DNA, RNA, ribosomes and enzymes. Protein synthesis and other reactions have been demonstrated inside liposomes. Non-lipidic compartments and non-biological components may also be used. SCs are used to generate basic knowledge about subjects such as origins-of-life and conditions for life and for applied technologies like smart drug delivery and drug screening.

The construction of a living SC is the Holy Grail of SC research. The term living would mean a SC would have the capacity of autonomous self-sustainment in an out-of-equilibrium homeostatic state, with the additional possibility of growth and division which could give rise to a minimal life cycle and evolution. As of 2019 SCs superficially resemble biological cells but their complexity is low. These SCs have a cell-like structure an perform some life-like operations.

SCs fall along the non-life/life transition path and are useful for modelling primitive compartments which are thought to be the precursors to primitive living cells. The likeness of SCs to machines in terms of programmability, modularity and orthogonality make them good tools for biotechnology, therapeutics and diagnostics.

SCs came out of synthetic biology after the 2000s but program of SC construction by assembling separated molecules was defined in the 1990s. This approach was promoted by origins-of-life researchers including Pier Luigi Luisi at ETH-Zürich. Origin-of-life SC research flowed into synthetic biology around the 2000s, bringing together other research lines for “bottom-up” synthetic biology, which is sometimes called “cell-free”, “in vitro” or “chemical” synthetic biology.

The idea of encapsulating solutes inside liposomes has earlier roots including the enzyme-containing coacervates described by A.I. Oparin in 1965. A coacervate is a spherical aggregation of lipid molecules that makes up a colloidal inclusion held together by hydrophobic forces, that can measure 1 to 100 micrometers in diameter. Oparin suggested that coacervates may have played a significant role in the evolution of cells. Coacervates form spontaneously when a protein such as gelatin reacts with gum arabic. Coacervates provide a locally segregated environment that also allows selective adsorption of simple organic molecules from the surrounding medium.