Investigating Prebiotic Protocells for A Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective

Abstract

Protocells are supramolecular systems commonly used for numerous applications, such as the formation of self-evolvable systems, in systems chemistry and synthetic biology. Certain types of protocells imitate plausible prebiotic compartments, such as giant vesicles, that are formed with the hydration of thin films of amphiphiles. These constructs can be studied to address the emergence of life from a non-living chemical network. They are useful tools since they offer the possibility to understand the mechanisms underlying any living cellular system: Its formation, its metabolism, its replication and its evolution. Protocells allow the investigation of the synergies occurring in a web of chemical compounds. This cooperation can explain the transition between chemical (inanimate) and biological systems (living) due to the discoveries of emerging properties. The aim of this review is to provide an overview of relevant concept in prebiotic protocell research.

Keywords: compartment; origin of life; prebiotic chemistry; protocell; systems chemistry.

Figure 1

The formamide clue studied during the last 20 years by Saladino and colleagues. Amino acids (in blue), nucleobases and lipid precursors (not shown) can notably be produced by combination of formamide (in red) and other small carbon based molecules.

Figure 2

A summary of some plausible prebiotic routes for the formation of aminoacids, nucleic acids and phospholipids from common building blocks. Prebiotic synthesis of phospholipids and other amhiphiles was summarized elsewhere [24].

Figure 3

The structure of some amphiphiles that have been studied as first protocells membrane constituents: (A) Different mono- and dialkyl phosphates structures; (B) a general structure of a fatty acid; (C) The structure of ester and ether phospholipids.

Figure 4

The spontaneous appearance of closed membranes composed of bilayers of self-assembling amphiphiles was likely a prerequisite for Darwinian competitive behavior to set in at the molecular level. Such compartments should be dynamic in their membrane composition (evolvable), sufficiently stable to harbor macro-molecules, yet semi-permeable for reactive small molecules to get across the membrane and the content to be able to avoid chemical equilibrium.

Figure 5

(A) Hydrothermal vents on the bottom of Atlantic ocean; (B) A hydrothermal pool in Dallo (Africa); (C) Electron microscopic imagine of a clay mineral; (D) Stromatolite in western Australia. Public domain images.

Figure 6

The life cycle and evolution of the protocells. 1: Formation. Protocells can emerge from a mixture of compounds (1a) which are present in a specific medium with characteristic conditions such as T: Temperature, P: Pressure, pH (1b). 2: Metabolism. Functional protocells are able to exchange with the medium (2a) and they possess a source of energy (2b) which fuels a catalytic network (2c) producing products (P) and waste (W) from substrates (S). 3: Replication. Protocell division involves the replication of some of its content (3a) but also the replication of the container (3b). 4: Evolution. Through divisions, protocells can acquire new compounds involving a higher fitness for the systems (4a). These protocells are preferentially conserved during selection and evolution (4b). On the other hand, if a protocell does not keep the different acquired networks or has less efficient networks, then it will lose the competition, and in that case it is a dead end for the system (5). This figure was adapted from Kee et al., 2017 [51].

Figure 7

Schematic representation of vesicles self-reproduction. This process, already called growth and division, is a process in which a growing vesicle (a→b) first transforms its spherical shape into a dumbbell shape (b→c), and then splits into two spherical daughter vesicles (c→d). Budding, growth and pearling are some other processes part of the growth and division process, however not always clearly observable.

Figure 8

Preparation and use of DOPC SGVs (1) for the monitoring and analysis of the growth and division processes. (A) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, a), was anchored by first treating glass beads with avidin/biotin-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [biotinyl(polyethylene glycol)-2000], (b), then adding multilamellar DOPC vesicles from which a bilayer was transferred to coat the beads; a fluorescent lipidic probe the DOPE-Rh⁺ (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulphonyl) ammonium salt (c). (B) A supported DOPC giant vesicles (1, SGVs, grey circle filled blue) fed with oleic acid (OA, 2, orange) grow through incorporation of OA and divide into supported GVs (3, orange circles filled blue) and new unsupported vesicles (4, blue rings around yellow circles). The composition of the membranes of SGVs (3) and daughter GVs (4) was elucidated by chromatographic analysis associated with mass spectrometry or by the Stewart test [115].

Figure 9

The structure of the catalytic dipeptide SerHis and the membranogenic dipeptide AcPheLeuNH₂.