and her colleagues (2013) used X-ray diffraction to analyze mixtures of dehydrated self-assembled lipid multilamellar structures in the presence of a layer of mononucleotides such as adenosine monophosphate (AMP). The multilamellar structures are organizational structures, so condensation reactions of the mononucleotides into RNA-like polymers can thus occur (De Guzman et al. 2014; Misuraca et al. 2017).
Cell blanks were obtained by assembling phospholipids, amphiphilic molecules that interact through a hydrophilic head (which likes water) and a hydrophobic tail (which avoids any interaction with water). This structure allows organization in water in the form of vesicles. Researchers have shown that prebiotic compounds, such as polyprenyl phosphate, combine in water to form oriented double layers (Nakatani et al. 2014).
Jeff Errington (2013) followed the development of the Bacillus subtilis L-form (wall-free) bacterium and a liposome under the same conditions. Both bacteria and liposome split, fuse together and produce offspring in the form of small vesicles, which are morphologically very similar (see Figure 1.5). The unusual mode of proliferation of these bacteria by budding and fission could serve as a model for the in vitro simulation of vesicles or primitive cells. The binary fission mechanism provides insight into how early cell life forms were able to proliferate. Later in evolution, the invention of the protective cell wall may have been responsible for the expansion of bacterial life on Earth.
Figure 1.5. a) Proliferation of L-Bacillus subtilis. Courtesy of Jeff Errington. b) Liposome budding. Phospholipid vesicles in the presence of oleic acid. Courtesy of Primož Peterlin (2009)
Luisi and his collaborators were pioneers in the study of the processes by which lipid vesicles could develop and even reproduce (Walde et al. 1994a, 1994b; Luisi 2002, 2016). For example, it has been shown that when oleoyl anhydride was exposed to an aqueous buffer at alkaline pH, the anhydride was slowly hydrolyzed and the resulting oleic acid assembled into membrane vesicles. The vesicles can grow by the addition of fatty acids in the environment and then divide into smaller vesicles that grow, compete for resources, and even have a simple version of a feedback cycle that can regulate growth (Chen and Szostak 2004; Mansy and Szostak 2008; Adamala and Szostak 2013a, 2013b; Engelhart et al. 2016; Jimbo et al. 2016).
What can we deduce from these observations regarding our knowledge of the reproduction of the ancestors of today’s bacteria?
Briers et al. (2012) studied the gap between the first protocell and the hypothetical cell ancestor named “Luca”. Although there are striking coincidences between the two behaviors, the similarities observed still deserve long studies to confirm an ancestral morphological link and the understanding of the origins of unicellular life.
1.6. Rebuilding a living cell: a wide range of possibilities explored, from the mineral to the organic
Today, we speak of “chemical gardens” and “metallic vegetation” to refer to self-organized chemical figures that evoke plant diversity. When a metal salt is brought into contact with a basic aqueous solution of silicate, carbonate or phosphate, patterns called “flowers” are produced in the laboratory (Haudin et al. 2018). Technological innovations are suggested by these natural mineral productions which flourish today in the field of biomimicry. They find multiple biophysical, robotic, electronic, automatic, aeronautical, architectural, etc. applications, with the purpose of compensating for our weaknesses and repairing handicaps. Let us note here that mimicry is not the prerogative of modern technologies. A spider can be mistaken, even by the greatest arachnologist, for a fragment of a dead leaf.
The mechanobiology of biological membranes has become a growing field of research, particularly in the field of synthetic biology, towards artificial cells with genetic circuits and reaction cascades. Maximizing the modularity of their design and their flexibility is made possible by encapsulating them in liposomes, allowing chemical reactions to take place in well isolated environments. Such minimal synthetic cells, called “synells”, were designed by MIT researchers3 , who founded Synlife in 2017. They are governed by external signals and communication between liposomes, which can be fused in a controlled manner (Adamala et al. 2016).
Artificial life, in silico, a new paradigm between the machine and the living, serves as a model for the design of mineral “creatures”, organoids, automata (mechanical or bionic), micro-robots with metabolisms (Hamada et al. 2019), humanoids, etc., which would “emerge” from nanotechnology. The pairing of the brain and machine aims at the illusory perfection of the human species aspiring, as described by Aldous Huxley in 1932 in Brave New World, to impose its path to evolution.
1.7. Conclusion
Seeking to understand how life appeared on Earth also means looking for the fossil traces of the first cells, which inevitably leads to the question of how big the smallest living organism is (implied: the smallest being the simplest, therefore the first to appear on Earth). In connection with genomics work, Craig Venter (director of the Institute for Genomic Research – TIGR4 – in Rockville, Maryland) and Hamilton Smith (who won the Nobel Prize in 1978 for the co-discovery of restriction enzymes) have removed the genes of Mycoplasma genitalium one by one, reputed to have the smallest known genome. The aim is to obtain a viable organism with the minimum number of genes, Mycoplasma laboratorium, making it possible to develop, in fine, the smallest living organism possible: “The goal is to fundamentally understand the components of the most basic living cell” (Singer 2007). This approach raises one of the most delicate problems in contemporary biology: what consequences can the manufacture of such objects have on the future of humanity, the biosphere, the environment and the planet? Is there a risk of unbalancing ecosystems?
Producing organisms that are “outside the norm”, in the technical sense, employs us to think about the standardization of criteria for living things, the quality of life, and lastly, the normativity of living things (what does “being normal” mean?). In 1995, Jean-Pierre Séris declared that it was impossible to set standards of vital value: “Uniformity, the reproduction of that which is identical has a meaning and a technical value. It has no biological value. It is biological nonsense ...”
1.8. Acknowledgements
Our thanks go to Ariel Anbar, Jeff Errington, Primož Peterlin, Pierre Thomas and Peter Walde, who kindly provided us with the figures and photographs (Figures 1.1 to 1.5), and to Jacques Vergne and Louis Ter-Ovanessian for their careful reading.
1.9. References
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Adamala, K.P., Martin-Alarcon, D.A., Guthrie-Honea, K.R., Boyden, E.S. (2016). Engineering genetic circuit interactions within and between synthetic minimal cells. Nature Chemistry, 9, 431–439.
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