Colony-like Protocell Superstructures

We report the formation, growth, and dynamics of model protocell superstructures on solid surfaces, resembling single cell colonies. These structures, consisting of several layers of lipidic compartments enveloped in a dome-shaped outer lipid bilayer, emerged as a result of spontaneous shape transformation of lipid agglomerates deposited on thin film aluminum surfaces. Collective protocell structures were observed to be mechanically more stable compared to isolated spherical compartments. We show that the model colonies encapsulate DNA and accommodate non-enzymatic, strand displacement DNA reactions. The membrane envelope is able to disassemble and expose individual daughter protocells, which can migrate and attach via nano-tethers to distant surface locations, while maintaining their encapsulated contents. Some colonies feature ‘exo-compartments’, which spontaneously extend out of the enveloping bilayer, internalize DNA, and merge again with the superstructure. A continuum elastohydrodynamic theory that we developed reveals that the subcompartment formation must be governed by attractive van der Waals (vdW) interactions between the membrane and surface. The balance between membrane bending and vdW interactions yields a critical length scale of 273 nm, above which the membrane invaginations can form subcompartments. The findings support our hypotheses that in extension of the ‘lipid world hypothesis’, protocells may have existed in the form of colonies, potentially benefiting from the increased mechanical stability provided by a superstructure.

Spontaneous formation of prebiotic compartment colonies on Hadean Earth and pre-Noachian Mars

The primitive cells that emerged at the origin of life are commonly viewed as spherical biosurfactant shells, freely suspended in aqueous media (1-3). This model explains initial, but not subsequent events in the development process towards structured protocells. Taking into consideration the involvement of naturally occurring surfaces, which were abundant on the early Earth (4), we report feasible and productive pathways for the development of primitive cells. Surfaces intrinsically possess energy, easily utilized by the interfacing amphiphiles, such as lipids, to attain self-organization and spontaneous transformations (5-7). We show that the physical interaction of phospholipid pools with 20 Hadean Earth analogue materials as well as a Martian meteorite composed of fused regolith representing the ancient crust of Mars, consistently lead to the shape transformation and autonomous formation of surfactant compartment assemblies. Dense, colony-like protocell populations grow from these lipid deposits, predominantly at the grain boundaries or cleavages of the investigated natural surfaces, and remain there for several days. The model protocells in our study are able to autonomously develop, transform and pseudo-divide, and encapsulate RNA as well as DNA. We also demonstrate that they can accommodate non-enzymatic, DNA strand displacement reactions. Our findings suggest a feasible route towards the transformation from non-living to living entities, and provide fresh support for the 'Lipid World' hypothesis (8).

Lipid-Assisted Polymerization of Nucleotides

In addition to being one of the proponents of the “Lipid World hypothesis”, David Deamer, together with other colleagues, pioneered studies involving formation of RNA-like oligomers from their ‘non-activated’, prebiotically plausible monomeric moieties. In particular, the pioneering work in this regard was a publication from 2008 in Origins of Life and Evolution of Biospheres, The Journal of the International Astrobiology Society, wherein we described the formation of RNA-like oligomers from nucleoside 5’-monophosphates. In that study, we had simulated a terrestrial geothermal environment, a niche that is thought to have facilitated the prebiotic non-enzymatic synthesis of polynucleotides. We showed that a mixture of lipids and non-activated mononucleotides resulted in the formation of relatively long strands of RNA-like polymers when subjected to repeated cycles of dehydration and rehydration (DH-RH). Since 2008, terrestrial geothermal niches and DH-RH conditions have been explored in the context of several other prebiotic processes. In this article, we review the work that we and other researchers have carried out since then in this line of research, including the development of new apparatus to carry out the simulation of prebiotic terrestrial geothermal environments.

Twenty Years of “Lipid World”: A Fertile Partnership with David Deamer

“The Lipid World” was published in 2001, stemming from a highly effective collaboration with David Deamer during a sabbatical year 20 years ago at the Weizmann Institute of Science in Israel. The present review paper highlights the benefits of this scientific interaction and assesses the impact of the lipid world paper on the present understanding of the possible roles of amphiphiles and their assemblies in the origin of life. The lipid world is defined as a putative stage in the progression towards life’s origin, during which diverse amphiphiles or other spontaneously aggregating small molecules could have concurrently played multiple key roles, including compartment formation, the appearance of mutually catalytic networks, molecular information processing, and the rise of collective self-reproduction and compositional inheritance. This review brings back into a broader perspective some key points originally made in the lipid world paper, stressing the distinction between the widely accepted role of lipids in forming compartments and their expanded capacities as delineated above. In the light of recent advancements, we discussed the topical relevance of the lipid worldview as an alternative to broadly accepted scenarios, and the need for further experimental and computer-based validation of the feasibility and implications of the individual attributes of this point of view. Finally, we point to possible avenues for exploring transition paths from small molecule-based noncovalent structures to more complex biopolymer-containing proto-cellular systems.

Possible Roles of Amphiphilic Molecules in the Origin of Biological Homochirality

A review. The question of homochirality is an intriguing problem in the field of chemistry, and is deeply related to the origin of life. Though amphiphiles and their supramolecular assembly have attracted less attention compared to biomacromolecules such as RNA and proteins, the lipid world hypothesis sheds new light on the origin of life. This review describes how amphiphilic molecules are possibly involved in the scenario of homochirality. Some prebiotic conditions relevant to amphiphilic molecules will also be described. It could be said that the chiral properties of amphiphilic molecules have various interesting features such as compositional information, spontaneous formation, the ability to exchange components, fission and fusion, adsorption, and permeation. This review aims to clarify the roles of amphiphiles regarding homochirality, and to determine what kinds of physical properties of amphiphilic molecules could have played a role in the scenario of homochirality.

Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

Systems chemistry has been a key component of origin of life research, invoking models of life’s inception based on evolving molecular networks. One such model is the graded autocatalysis replication domain (GARD) formalism embodied in a lipid world scenario, which offers rigorous computer simulation based on defined chemical kinetics equations. GARD suggests that the first pre-RNA life-like entities could have been homeostatically-growing assemblies of amphiphiles, undergoing compositional replication and mutations, as well as rudimentary selection and evolution. Recent progress in molecular dynamics has provided an experimental tool to study complex biological phenomena such as protein folding, ligand-receptor interactions, and micellar formation, growth, and fission. The detailed molecular definition of GARD and its inter-molecular catalytic interactions make it highly compatible with molecular dynamics analyses. We present a roadmap for simulating GARD’s kinetic and thermodynamic behavior using various molecular dynamics methodologies. We review different approaches for testing the validity of the GARD model by following micellar accretion and fission events and examining compositional changes over time. Near-future computational advances could provide empirical delineation for further system complexification, from simple compositional non-covalent assemblies towards more life-like protocellular entities with covalent chemistry that underlies metabolism and genetic encoding.

Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

Systems Chemistry has been a key component of origin of life research, invoking models of life’s inception based on evolving molecular networks. One such model is the Graded Autocatalysis Replication Domain (GARD) formalism embodied in a Lipid World scenario, which offers rigorous computer simulation based on defined chemical kinetics equations. GARD suggests that the first pre-RNA life-like entities could have been homeostatically-growing assemblies of amphiphiles, undergoing compositional replication and mutations, as well as rudimentary selection and evolution. Recent progress in Molecular Dynamics has provided an experimental tool to study complex biological phenomena such as protein folding, ligand-receptor interactions and micellar formation, growth and fission. The detailed molecular definition of GARD and its inter-molecular catalytic interactions make it highly compatible with Molecular Dynamics analyses. We present a roadmap for simulating GARD’s kinetic and thermodynamic behavior using various Molecular Dynamics methodologies. We review different approaches for testing the validity of the GARD model, by following micellar accretion and fission events and examining compositional changes over time. Near future computational advances could provide empirical delineation for further system complexification, from simple compositional non-covalent assemblies towards more life-like protocellular entities with covalent chemistry that underlies metabolism and genetic encoding.