Following is a synthetic review on the minimal living cell, defined as an artificial or a semi-artificial cell having the minimal and sufficient number of components to be considered alive. We describe concepts and experiments based on these constructions, and we point out that an operational definition of minimal cell does not define a single species, but rather a broad family of interrelated cell-like structures. The relevance of these researches, considering that the minimal cell should also correspond to the early simple cell in the origin of life and early evolution, is also explained. In addition, we present detailed data in relation to minimal genome, with observations cited by several authors who agree on setting the theoretical full-fledged minimal genome to a figure between 200 and 300 genes. However, further theoretical assumptions may significantly reduce this number (i.e. by eliminating ribosomal proteins and by limiting DNA and RNA polymerases to only a few, less specific molecular species). Generally, the experimental approach to minimal cells consists in utilizing liposomes as cell models and in filling them with genes/enzymes corresponding to minimal cellular functions. To date, a few research groups have successfully induced the expression of single proteins, such as the green fluorescence protein, inside liposomes. Here, different approaches are described and compared. Present constructs are still rather far from the minimal cell, and experimental as well as theoretical difficulties opposing further reduction of complexity are discussed. While most of these minimal cell constructions may represent relatively poor imitations of a modern full-fledged cell, further studies will begin precisely from these constructs. In conclusion, we give a brief outline of the next possible steps on the road map to the minimal cell.

The bottom-up branch of synthetic biology includes—among others—innovative studies that combine cell-free protein synthesis with liposome technology to generate cell-like systems of minimal complexity, often referred to as synthetic cells. The functions of this type of synthetic cell derive from gene expression, hence they can be programmed in a modular, progressive and customizable manner by means of ad hoc designed genetic circuits. This experimental scenario is rapidly expanding and synthetic cell research already counts numerous successes. Here, we present a review focused on the exchange of chemical signals between liposome-based synthetic cells (operating by gene expression) and biological cells, as well as between two populations of synthetic cells. The review includes a short presentation of the “molecular communication technologies,” briefly discussing their promises and challenges.

Supramolecular chemistry was enriched, about twenty years ago, by the discovery of the self-reproduction of micelles and vesicles. The dynamic aspects and complexity of these systems makes them good models for biological compartments. For example, the self-reproduction of vesicles suggests that the growth in size and number of a vesicle population resembles the pattern of living cells in several aspects, but it take place solely due to physical forces. Several reports demonstrate that reverse micelles, micelles, sub-micrometric and giant vesicles can self-reproduce, generating new particles at the expenses of a suitable precursor. Recently, similar studies are in progress on more complex vesicle-based systems, namely semi–synthetic minimal cells. These are artificial cell–like compartments that are built by filling liposomes with the minimal number of biomolecules, such as DNA, ribosomes, enzymes, etc., in order to construct a living cell in the laboratory. This approach aims to investigate the minimal requirements for molecular systems in order to display some living properties, while it finds relevance in origins of life studies and in synthetic (constructive) biology.