How early cell membranes may have shaped 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.

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. 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.

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 destabilised or fragmented, requiring structural reorganisation upon thawing. The loosely packed lateral organisation 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, researcher at ELSI.

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 recognise 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 the 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. 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 destabilised 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 realised 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.

Reference

Tatsuya Shinoda¹, Natsumi Noda², Takayoshi Watanabe^2,3, Kazumu Kaneko⁴, Yasuhito Sekine², and Tomoaki Matsuura*², Compositional selection of phospholipid compartments in icy environments drives the enrichment of encapsulated genetic information, Chemical Science, DOI: 10.1039/d5sc04710b

1. Department of Life Science and Technology, Institute of Science Tokyo, Japan
2. Earth-Life Science Institute (ELSI), Institute of Science Tokyo, Tokyo 152-8550, Japan
3. MAQsys Inc., Kanagawa 213-0012, Japan
4. Department of Earth and Planetary Sciences, Institute of Science Tokyo, Tokyo 152-8550, Japan

More information

Earth-Life Science Institute (ELSI) is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and collaborate on the most challenging scientific problems. ELSI’s primary aim is to address the origin and co-evolution of the Earth and life.

Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”

World Premier International Research Center Initiative (WPI) was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).