Prebiotic chemists often study how modern biopolymers, e.g., peptides and nucleic acids, could have originated in the primitive environment, though most contemporary biomonomers don't spontaneously oligomerize under mild conditions without activation or catalysis. However, life may not have originated using the same monomeric components that it does presently. There may be numerous non-biological (or "xenobiological") monomer types that were prebiotically abundant and capable of facile oligomerization and self-assembly. Many modern biopolymers degrade abiotically preferentially via processes which produce thermodynamically stable ring structures, e.g. diketopiperazines in the case of proteins and 2', 3'-cyclic nucleotide monophosphates in the case of RNA. This weakness is overcome in modern biological systems by kinetic control, but this need not have been the case for primitive systems. We explored here the oligomerization of a structurally diverse set of prebiotically plausible xenobiological monomers, which can hydrolytically interconvert between cyclic and acyclic forms, alone or in the presence of glycine under moderate temperature drying conditions. These monomers included various lactones, lactams and a thiolactone, which varied markedly in their stability, propensity to oligomerize and apparent modes of initiation, and the oligomeric products of some of these formed self-organized microscopic structures which may be relevant to protocell formation.
The Panspermia hypothesis posits that either life's building blocks (molecular Panspermia) or life itself (organism-based Panspermia) may have been interplanetarily transferred to facilitate the origins of life (OoL) on a given planet, complementing several current OoL frameworks. Although many spaceflight experiments were performed in the past to test for potential terrestrial organisms as Panspermia seeds, it is uncertain whether such organisms will likely "seed" a new planet even if they are able to survive spaceflight. Therefore, rather than using organisms, using abiotic chemicals as seeds has been proposed as part of the molecular Panspermia hypothesis. Here, as an extension of this hypothesis, we introduce and review the plausibility of a polymeric material-based Panspermia seed (M-BPS) as a theoretical concept, where the type of polymeric material that can function as a M-BPS must be able to: (1) survive spaceflight and (2) "function", i.e., contingently drive chemical evolution toward some form of abiogenesis once arriving on a foreign planet. We use polymeric gels as a model example of a potential M-BPS. Polymeric gels that can be prebiotically synthesized on one planet (such as polyester gels) could be transferred to another planet via meteoritic transfer, where upon landing on a liquid bearing planet, can assemble into structures containing cellular-like characteristics and functionalities. Such features presupposed that these gels can assemble into compartments through phase separation to accomplish relevant functions such as encapsulation of primitive metabolic, genetic and catalytic materials, exchange of these materials, motion, coalescence, and evolution. All of these functions can result in the gels' capability to alter local geochemical niches on other planets, thereby allowing chemical evolution to lead to OoL events.
The sun generates light and heat for life on Earth to flourish. However, during the late Hadean-early Archean epoch on Earth, the "faint young sun" (FYS) was less luminous, influencing prebiotic chemistry and, by extension, the origins of life (OoL). However, higher levels of ultraviolet (UV) radiation from the FYS, especially UV-C, due to the lack of an ozone layer, would likely have impacted the assembly, stability, persistence, and functions of prebiotic cellular precursors, i.e., protocells. Consequently, it is essential to study how such UV-C radiation would have affected the synthesis and stability of prebiotically relevant molecules and protocells to better understand the plausibility of the OoL during the FYS period. In this letter, we introduce unanswered questions surrounding the structure and stability of protocells under UV-C radiation. Such a perspective may be vital to exoplanetary systems orbiting other stars, enhancing our understanding of life's potential beyond our solar system.
Compartmentalization was likely essential for primitive chemical systems during the emergence of life, both for preventing leakage of important components, i.e., genetic materials, and for enhancing chemical reactions. Although life as we know it uses lipid bilayer-based compartments, the diversity of prebiotic chemistry may have enabled primitive living systems to start from other types of boundary systems. Here, we demonstrate membraneless compartmentalization based on prebiotically available organic compounds, α-hydroxy acids (αHAs), which are generally coproduced along with α-amino acids in prebiotic settings. Facile polymerization of αHAs provides a model pathway for the assembly of combinatorially diverse primitive compartments on early Earth. We characterized membraneless microdroplets generated from homo- and heteropolyesters synthesized from drying solutions of αHAs endowed with various side chains. These compartments can preferentially and differentially segregate and compartmentalize fluorescent dyes and fluorescently tagged RNA, providing readily available compartments that could have facilitated chemical evolution by protecting, exchanging, and encapsulating primitive components. Protein function within and RNA function in the presence of certain droplets is also preserved, suggesting the potential relevance of such droplets to various origins of life models. As a lipid amphiphile can also assemble around certain droplets, this further shows the droplets' potential compatibility with and scaffolding ability for nascent biomolecular systems that could have coexisted in complex chemical systems. These model compartments could have been more accessible in a "messy" prebiotic environment, enabling the localization of a variety of protometabolic and replication processes that could be subjected to further chemical evolution before the advent of the Last Universal Common Ancestor.
Nucleic acid segregation and compartmentalization were likely essential functions that primitive compartment systems resolved during evolution. Recently, polyester microdroplets generated from dehydration synthesis of various α-hydroxy acids (αHA) were suggested as potential primitive compartments. Some of these droplets can differentially segregate and compartmentalize organic dyes, proteins, and nucleic acids. However, the previously studied polyester microdroplets included limited αHA chemical diversity, which may not reflect the chemical diversity available in the primitive Earth environment. Here, we increased the chemical diversity of polyester microdroplet systems by combinatorially adding an αHA monomer with a basic side chain, 4-amino-2-hydroxybutyric acid (4a2h), which was incorporated with different ratios of other αHAs containing uncharged side chains to form combinatorial heteropolyesters via dehydration synthesis. Incorporation of 4a2h in the polymers resulted in the assembly of some polyester microdroplets able to segregate fluorescent RNA or potentially acquire intrinsic fluorescent character, suggesting that minor modifications of polyester composition can significantly impact the functional properties of primitive compartments. This study suggests one process by which primitive chemical systems can increase diversity of compartment "phenotype" through simple modifications in their chemical composition.
All life on Earth is composed of cells, which are built from and run by biological reactions and structures. These reactions and structures are generally the result of action by cellular biomolecules, which are indispensable for the function and survival of all living organisms. Specifically, biological catalysis, namely by protein enzymes, but also by other biomolecules including nucleic acids, is an essential component of life. How the biomolecules themselves that perform biological catalysis came to exist in the first place is a major unanswered question that plagues researchers to this day, which is generally the focus of the origins of life (OoL) research field. Based on current knowledge, it is generally postulated that early Earth was full of a myriad of different chemicals, and that these chemicals reacted in specific ways that led to the emergence of biochemistry, cells, and later, life. In particular, a significant part of OoL research focuses on the synthesis, evolution, and function of biomolecules potentially present under early Earth conditions, as a way to understand their eventual transition into modern life. However, this narrative overlooks possibilities that other molecules contributed to the OoL, as while biomolecules that led to life were certainly present on early Earth, at the same time, other molecules that may not have strict, direct biological lineage were also widely and abundantly present. For example, hydroxy acids, although playing a role in metabolism or as parts of certain biological structures, are not generally considered to be as essential to modern biology as amino acids (a chemically similar monomer), and thus research in the OoL field tends to perhaps focus more on amino acids than hydroxy acids. However, their likely abundance on early Earth coupled with their ability to spontaneously condense into polymers (i.e., polyesters) make hydroxy acids, and their subsequent products, functions, and reactions, a reasonable target of investigation for prebiotic chemists. Whether "non-biological" hydroxy acids or polyesters can contribute to the emergence of life on early Earth is an inquiry that deserves attention within the OoL community, as this knowledge can also contribute to our understanding of the plausibility of extraterrestrial life that does not exactly use the biochemical set found in terrestrial organisms. While some demonstrations have been made with respect to compartment assembly, compartmentalization, and growth of primitive polyester-based systems, whether these "non-biological" polymers can contribute any catalytic function and/or drive primitive reactions is still an important step toward the development of early life. Here, we review research both from the OoL field as well as from industry and applied sciences regarding potential catalysis or reaction driven by "non-biological" polyesters in various forms: as linear polymers, as hyperbranched polyesters, and as membraneless microdroplets.
Polyester microdroplets have been investigated as primitive protocell models that can exhibit relevant primitive functions such as biomolecule segregation, coalescence, and salt uptake. Such microdroplets assemble after dehydration synthesis of alpha-hydroxy acid (αHA) monomers, commonly available on early Earth, via heating at mild temperatures, followed by rehydration in aqueous media. αHAs, in particular, are also ubiquitous in biology, participating in a variety of biochemical processes such as metabolism, suggesting the possible strong link between primitive and modern αHA-based processes. Although some primitive αHA polymerization conditions have been probed previously, including monomer chirality and reaction temperature, relevant factors pertaining to early Earth's local environmental conditions that would likely affect primitive αHA polymerization are yet to be fully investigated. Hence, probing the entire breadth of possible conditions that could promote primitive αHA polymerization is required to understand the plausibility of polyester microdroplet assembly on early Earth at the origin of life. In particular, there are numerous aqueous environments available on early Earth that could have resulted in varying volumes and concentrations of αHA accumulation, which would have affected subsequent αHA polymerization reactions. Similarly, there were likely varying levels of salt in the various aqueous prebiotic solutions, such as in the ocean, lakes, and small pools, that may have affected primitive reactions. Here, we probe the limits of the dehydration synthesis and subsequent membraneless microdroplet (MMD) assembly of phenyllactic acid (PA), a well-studied αHA relevant to both biology and prebiotic chemistry, with respect to reactant concentration and volume and salinity through mass spectrometry- and microscopy-based observations. Our study showed that polymerization and subsequent microdroplet assembly of PA appear robust even at low reactant concentrations, smaller volumes, and higher salinities than those previously tested. This indicates that PA-polyester and its microdroplets are very much viable under a wide variety of conditions, thus more likely participating in prebiotic chemistries at the origins of life.
α-Hydroxy acids are prebiotic monomers that undergo dehydration synthesis to form polyester gels, which assemble into membraneless microdroplets upon aqueous rehydration. These microdroplets are proposed as protocells that can segregate and compartmentalize primitive molecules/reactions. Different primitive aqueous environments with a variety of salts could have hosted chemistries that formed polyester microdroplets. These salts could be essential cofactors of compartmentalized prebiotic reactions or even directly affect protocell structure. However, fully understanding polyester-salt interactions remains elusive, partially due to technical challenges of quantitative measurements in condensed phases. Here, spectroscopic and biophysical methods are applied to analyze salt uptake by polyester microdroplets. Inductively coupled plasma mass spectrometry is applied to measure the cation concentration within polyester microdroplets after addition of chloride salts. Combined with methods to determine the effects of salt uptake on droplet turbidity, size, surface potential and internal water distribution, it was observed that polyester microdroplets can selectively partition salt cations, leading to differential microdroplet coalescence due to ionic screening effects reducing electrostatic repulsion forces between microdroplets. Through applying existing techniques to novel analyses related to primitive compartment chemistry and biophysics, this study suggests that even minor differences in analyte uptake can lead to significant protocellular structural change.
α-hydroxy acids (αHAs), simple and prebiotically plausible organic monomers, were likely present in various environments on and off Earth and could have played a role in directing the emergence of the first homochiral living systems. Some αHAs, which could have been of varying chirality, can undergo dehydration polymerization into polyesters, which could assemble into membraneless microdroplets upon rehydration; understanding these processes is critical for unraveling how simple prebiotic molecules transitioned into more complex systems capable of supporting selective chemical reactions, a key step toward the origin of life. Here, we focused on tartaric acid (TA), a prebiotically relevant αHA with multiple chiral forms, to probe plausible mechanisms by which primitive αHA and polyester-based systems could have participated in selective homochiral polymer synthesis. Enantiopure solutions of d-TA or l-TA polymerize efficiently via dehydration, while racemic dl-TA polymerization is inhibited due to stereochemical incompatibility. We found that Ca2+ ions influence this process in two significant ways: 1) regulating TA monomer availability through selective crystallization, removing equal amounts of both enantiomers in racemic proportion and thereby enriching the enantiomeric excess of the remaining nonracemic TA solution; and 2) modulating polymerization by suppressing enantiopure TA polymerization while enabling dl-TA polymerization. These findings suggest that the differential availability of simple inorganic ions, such as Ca2+, could have indirectly mediated the selection of simple organic chiral monomers and the emergence of homochirality in primitive protocell-forming polymers, offering a pathway from nonliving to living matter in early Earth environments.