Expanding roles for diverse physical phenomena during the origin of life

Abstract

Recent synthetic approaches to understanding the origin of life have yielded insights into plausible pathways for the emergence of the first cells. Here we review current experiments with implications for the origin of life, emphasizing the ability of unexpected physical processes to facilitate the self-assembly and self-replication of the first biological systems. These laboratory efforts have uncovered novel physical mechanisms for the emergence of homochirality; the concentration and purification of prebiotic building blocks; and the ability of the first cells to assemble, grow, divide, and acquire greater complexity. In the absence of evolved biochemical capabilities, such physical processes likely played an essential role in early biology.

Figure 1

Physical mechanisms of chiral amplification based on phase transitions. (A) Schematic of processes involved in crystal grinding experiments. Abrasive grinding of a racemic slurry of L and D crystals with glass beads leads to the amplification of an initially small ee to a nearly-homochiral state. Identical processes occur for crystals of both L (left) and D (right) enantiomers, with rapid solution phase racemization (purple arrows) maintaining a racemic pool of monomers in solution. Abrasive grinding and dissolution lead to large crystals breaking into smaller crystals which eventually dissolve into chiral monomers. Growth by monomer addition occurs preferentially on larger crystals due to their lower surface energy compared to smaller crystals. A second-order pathway for growth by the addition of small crystal clusters (green, dashed arrow) has been proposed to explain the inexorable drive to homochirality. (B) Enantioenrichment of compounds that crystallize as a racemate. If a solution with an initial ee (left) is concentrated, crystallization of the racemate (right) leaves monomers of the chirality that is in excess in solution, because conglomerate (chiral) crystals are energetically disfavored relative to crystals of the racemate. Therefore, the solution phase becomes highly enriched in the chirality of the initial ee.

Figure 2

Schematic for nucleic acid oligomer purification by liquid crystal formation. (A) A heterogeneous population of single-stranded oligomers contains some strands (blue) that can assemble to form duplex segments, and an excess of non-functional strands (red, green, and brown) that cannot form duplexes due to incorrect linkages, modified bases, or the incorporation of L nucleotides. (B) Below the melting temperature of the oligomers, duplex forming strands hybridize to complementary sequences and form short double-stranded helices. (C) At sufficient concentrations, the short double-stranded nucleic acids phase separate into liquid crystal droplets due to preferential co-axial stacking and depletion forces from the single strands in solutions.

Figure 3

Molecular concentration by thermal diffusion columns in a hydrothermal vent setting. (A) Image (left, scale bar represents 3.5 cm) of a vent chimney (composed of calcium carbonate) taken from the Lost City alkaline hydrothermal field. Cross-sectional micrographs (right, scale bar represents 500 μm) show that the rock contains numerous pores and channels, which are proximal to both hot vent water and cold ocean water. Such structures have been proposed to act as sites for natural thermal diffusion columns. Figure modified, with permission, from Reference . (B) Schematic for a thermal diffusion column. A lateral temperature gradient across a vertical channel induces convective flow (dashed line) due to buoyancy effects. Thermophoresis (solid lines) also occurs along the direction of the temperature gradient. The coupling of these two processes can lead to significant concentration of selected molecular species towards the bottom of the channel. (C) Schematic for the assembly of cell-like structures from a dilute prebiotic reservoir in a thermal diffusion column. Prebiotic chemical processes generate a dilute solution containing simple lipids, which exist as monomers or micelles at low concentrations, and nucleic acids (represented as green helices) (left). A temperature gradient causes both components to become concentrated. Once their concentration exceeds a characteristic threshold (below the dashed line), the lipids self-assemble into bilayer vesicles, which encapsulate the concentrated nucleic acids in the solution (right).

Figure 4

Schematic of the dynamic processes intrinsic to fatty acid membrane systems. (A) Comparison of the chemical structures of phospholipids, the major constituent of modern cell membranes, and fatty acids, which have been proposed to serve an analogous role in primitive cell membranes. Phospholipids feature complex, charged head groups with a variety of possible functional groups (X) e.g. choline, glycerol, and serine. In contrast, fatty acids have a simple carboxylate as their hydrophilic head group. The smaller, easily neutralized carboxylate allows fatty acids to rapidly flip across the bilayer (B), which is crucial for the high permeability of fatty acid membranes. Fatty acids are also mono-acyl lipids, as opposed to di-acyl (di-alkyl for archaea) phospholipids, which increases their water solubility. Fatty acid bilayers are in equilibrium with significant concentrations of micelles and monomers in solution, with individual fatty acids rapidly transferring between these structures (C). This lipid phase polymorphism and dynamic exchange is essential for fatty acid vesicle growth and competition.

Figure 5

Coupled growth and division of fatty acid vesicles. (A) Schematic and (B–F) microscopy images of large (~4 μm) fatty acid vesicles undergoing growth and division. (B) Alkaline fatty acid micelles are added to a solution of initially spherical vesicles. (C, D) Rapid incorporation of the micelles causes the pre-formed vesicles to grow into long, filamentous structures at 10 and 25 minutes, respectively, after micelle addition. (E, F) Mild shear forces, such as solution agitation, cause the filamentous vesicles to break apart into many daughter vesicles, which can then undergo further rounds of growth and division. Vesicles were labeled by encapsulated fluorescent dye, which stays entrapped throughout the cycle. Scale bar represents 10 μm. Figure modified, with permission, from Reference .