Modern cells are intricate chemical entities, equipped with cytoskeletons, finely regulated molecules, and genetic material that governs nearly every aspect of their functioning. This complexity enables cells to thrive in diverse environments, competing based on their fitness. However, the earliest primordial cells were far simpler, consisting of small compartments where lipid membranes enclosed basic organic molecules. Bridging the gap between these simple protocells and complex modern cells is a major focus of research into the origin of life on Earth.
A new study conducted by researchers, including scientists at the Earth-Life Science Institute (ELSI) at the Institute of Science Tokyo, delves into how simple cell-like compartments behave under conditions that mimic early Earth. Instead of promoting a specific origin-of-life hypothesis, the study experimentally examines how variations in membrane composition affect protocell growth, fusion, and biomolecule retention during freeze-thaw cycles.
Exploring Protocell Growth and Membrane Composition
The research team investigated the impact of lipid composition on protocell growth by creating small spherical compartments known as large unilamellar vesicles (LUVs) using three types of phospholipids: POPC, PLPC, and DOPC. “We used phosphatidylcholine (PC) as membrane components due to their chemical structural continuity with modern cells, potential availability under prebiotic conditions, and ability to retain essential contents,” explained Tatsuya Shinoda, a doctoral student at ELSI and lead author of the study.
Despite their similarities, these molecules have crucial differences. POPC has one unsaturated acyl chain with a single double bond, PLPC contains one unsaturated acyl chain with two double bonds, and DOPC has two unsaturated acyl chains with one double bond each. As a result, POPC forms relatively rigid membranes, whereas PLPC and DOPC create more fluid membranes.
Freeze-Thaw Cycles and Membrane Dynamics
The LUVs underwent freeze-thaw cycles (F/T) to simulate temperature changes that affect protocells. After three F/T cycles, POPC-rich LUVs formed aggregates of closely packed vesicles, while PLPC- or DOPC-rich LUVs merged into larger compartments. The likelihood of vesicle merging and growth increased with higher PLPC content. “Under the stresses of ice crystal formation, membranes can become destabilized or fragmented, requiring structural reorganization upon thawing. The loosely packed lateral organization due to the higher degree of unsaturation may expose more hydrophobic regions during membrane reconstruction, facilitating interactions with adjacent vesicles and making fusion energetically favorable,” remarked Natsumi Noda, a researcher at ELSI.
Implications for the Origin of Life
What does this mean for the origin of life? When LUVs merge, their contents can mix and interact. In the primordial Earth’s “soup” of organic molecules, these fusion events might have brought crucial molecules together, enabling reactions that led to more cell-like structures. The team confirmed this by studying DNA retention in 100% POPC and 100% PLPC LUVs. PLPC vesicles not only captured DNA more effectively before F/T cycles but also retained more DNA than POPC vesicles with each cycle.
Dry-wet cycles on Earth’s surface and hydrothermal vents in the deep sea are popular theories for chemical and prebiotic evolution. This study suggests that icy environments might have also played a significant role. On primordial Earth, F/T cycles would have occurred over extended periods, with ice formation excluding solutes from growing crystals and increasing the local concentration of organic molecules and vesicles. Phospholipids with higher unsaturation degrees form more loosely packed membranes, facilitating vesicle fusion and content mixing. Conversely, more fluid phospholipid compartments can become destabilized under freeze-thaw stress, leading to leakage.
Evolutionary Considerations and Future Research
Permeability and stability are contradictory requirements, and the lipid composition of the “most fit” compartment would vary with environmental conditions. “A recursive selection of F/T-induced grown vesicles across successive generations may be realized by integrating fission mechanisms such as osmotic pressure or mechanical shear. With increasing molecular complexity, the intravesicular system, i.e., gene-encoded function, ultimately may take over the protocellular fitness, consequently leading to the emergence of a primordial cell capable of Darwinian evolution,” concludes Tomoaki Matsuura, Professor at ELSI and principal investigator of the study.
Reference: Tatsuya Shinoda, Natsumi Noda, Takayoshi Watanabe, Kazumu Kaneko, Yasuhito Sekine, and Tomoaki Matsuura, “Compositional selection of phospholipid compartments in icy environments drives the enrichment of encapsulated genetic information,” Chemical Science, DOI: 10.1039/d5sc04710b
This research not only sheds light on the potential conditions that facilitated the emergence of life but also opens new avenues for exploring the complex journey from simple molecules to living cells.
