How Early Cell Membranes Catalyzed the Origins of Life

Modern cells are complex chemical entities with cytoskeletons, finely regulated internal and external molecules, and genetic material that determines nearly every aspect of their functioning. This complexity allows cells to survive in a wide variety of environments and compete based on their fitness. However, the earliest primordial cells were little more than small compartments where a membrane of lipids enclosed simple organic molecules. Bridging the divide between simple protocells and complex modern cells is a major focus of research into the origin of life on Earth. New research explores protocell behavior A new study by a group of researchers, including scientists at the Earth-Life Science Institute (ELSI) at Institute of Science Tokyo, explores how simple cell-like compartments behave under physically realistic, non-equilibrium conditions relevant to early Earth. The research is published in the journal Chemical Science. Rather than advancing a specific origin-of-life hypothesis, the work experimentally examines how differences in membrane composition influence protocell growth, fusion, and the retention of biomolecules during freeze–thaw cycles. Investigating lipid composition and vesicle growth The research team studied the effect of lipid composition on protocell growth. The team created small spherical compartments called large unilamellar vesicles (LUVs) using three kinds of phospholipids: POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine; 16:0–18:1 PC), PLPC (1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine; 16:0–18:2 PC), and DOPC (1,2-di-oleoyl-sn-glycero-3-phosphocholine; 18:1 (D9-cis) PC). "We used phosphatidylcholine (PC) as membrane components, owing to their chemical structural continuity with modern cells, potential availability under prebiotic conditions, and retaining ability of essential contents," said Tatsuya Shinoda, a doctoral student at ELSI and lead author. However, there are small but crucial differences between these molecules. POPC has one unsaturated acyl chain with a single double bond. PLPC also contains one unsaturated acyl chain, but with two double bonds. DOPC has two unsaturated acyl chains with one double bond on each chain. As a result, POPC forms relatively rigid membranes, whereas PLPC and DOPC produce more fluid membranes. LUVs were then put through freeze/thaw cycles (F/T) to simulate temperature cycles that cause physical changes in protocells. After three F/T cycles, POPC-rich LUVs formed aggregates of many vesicles in close contact, whereas PLPC- or DOPC-rich LUVs merged to form much larger compartments. Vesicles were more likely to merge and grow as their PLPC content increased. These findings clearly show that phospholipids with more unsaturated bonds were more likely to merge and grow. "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," said Natsumi Noda, researcher at ELSI. Implications for the origin of life But what does this mean for the origin of life? When LUVs merge, their contents could mix and interact. In the "soup" of organic molecules on a primordial Earth, these fusion episodes might have brought important molecules together where they could react and become more like what we recognize as cells today. The team verified this by studying how well 100% POPC and 100% PLPC LUVs retained DNA. Not only were PLPC vesicles better at capturing DNA before F/T, but with each F/T cycle, they retained more DNA than POPC vesicles. Dry-wet cycles on Earth's surface and hydrothermal vents at the deep sea are the two most popular places where chemical and prebiotic evolution are believed to have taken place. The current study suggests that an icy environment might also have played an important role. On a primordial Earth, F/T cycles would take place over long periods. The formation of ice would exclude solutes from the growing ice crystals and increase the local concentration of organic molecules and vesicles. Balancing membrane stability and permeability Phospholipids with a higher degree of unsaturation form more loosely packed membranes, which facilitates vesicle fusion and content mixing. On the other hand, a compartment composed of more fluid phospholipids can become destabilized under freeze–thaw–induced stress, leading to leakage of its encapsulated contents. Permeability and stability are contradictory requirements, and the composition of the lipid compartment that is "most fit" would change based on 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 behind this study.