Spontaneous Crowding of Ribosomes and Proteins inside Vesicles: A Possible Mechanism for the Origin of Cell Metabolism

Abstract

One of the open questions in the origin of life is the spontaneous formation of primitive cell-like compartments from free molecules in solution and membranes. "Metabolism-first" and "replicator-first" theories claim that early catalytic cycles first evolved in solution, and became encapsulated inside lipid vesicles later on. "Compartment-first" theories suggest that metabolism progressively occurred inside compartments. Both views have some weaknesses: the low probability of co-entrapment of several compounds inside the same compartment, and the need to control nutrient uptake and waste release, respectively. By using lipid vesicles as early-cell models, we show that ribosomes, proteins and lipids spontaneously self-organise into cell-like compartments to achieve high internal concentrations, even when starting from dilute solutions. These findings suggest that the assembly of cell-like compartments, despite its low probability of occurrence, is indeed a physically realistic process. The spontaneous achievement of high local concentration might provide a rational account for the origin of primitive cellular metabolism.

Quasi-cellular systems: stochastic simulation analysis at nanoscale range

“…In this case, where multiple co-encapsulation events occur, the "anomalous entrapment" phenomenon (seen before for single molecular species [13,19]) acts by creating nanoscale liposomes containing hundreds of different molecules in a very small volume.…”

“…It is more difficult to perform similar studies in submicron vesicles, where it is expected, however, a higher diversity due to the enhancement of stochastic events at a smaller scale. Quite interestingly, two recent studies demonstrated that when 200 nm (diameter) lipid vesicles are prepared in presence of single macromolecular species, like ferritin [13] or ribosomes [14], the solute encapsulation does not follow the expected behavior. It resulted, instead, in a dramatic dichotomy between many "empty" vesicles and few "super-crowded" ones (having an internal solute concentration up to 60 times higher than the expected value).…”

The Encapsulation of Cell-free Transcription and Translation Machinery in Vesicles for the Construction of Cellular Mimics

“…The reconstitution of transcription-translation machinery from fully defined components 9 inside of vesicles 28 was particularly significant in facilitating later efforts in constructing environmentally responsive artificial cells17,18. Similarly, artificial cell studies have been used to probe evolutionary processes 4,29,30 , the mechanistic details of RNA and protein synthesis 22,31 , the influences of metabolic load32,33, and the assembly of viral particles 34 . Importantly, enough knowledge now exists that basic cellular function can be reconstituted inside of vesicles in the laboratory following these previous reports and the protocols described herein.…”

Small and Random Peptides: An Unexplored Reservoir of Potentially Functional Primitive Organocatalysts. The Case of Seryl-Histidine

“…In this context, it should be recalled that studies have shown that molecular crowding, which has been found in some vesicle systems [106,107,108], favors reverse proteolysis by volume exclusion effects [109]. The lipid membrane can favor growing reactions only inside the liposome lumen, owing to its semi-permeability, and provides a matrix for the peptide formation at the same time [110].…”