The missing link of evolution is often thought of as a step between apes and humans, but the biggest gap lies between non-living matter and the earliest living cells. A new study has found a mechanism that may have helped droplets transition into early cells, taking place in ponds, puddles and waterways that dried out and refilled repeatedly over time.

Cells are the base unit of life on Earth. From heart to skin to bacterial cells, they all have very different jobs, but a similar basic structure – namely, a membrane that protects the inside components from the outside environment while still allowing important molecules to pass in and out. But how these relatively complex structures came to be is still unknown.

The leading hypothesis at the moment starts with a mineral-rich mixture commonly called the primordial soup. This substance was made up of a cocktail of chemicals that reacted with each other fairly randomly, creating molecules such as RNA and amino acids. Then, with the help of a high-energy trigger like volcanic activity or lightning strikes, these could eventually start stacking the building blocks of life.

For the new study, the team investigated an alternative idea – instead of using the biological molecules we associate with life now, early life might have started by using different, very simple chemistry and evolved from there into cell-like structures.

Previous work by the team focused on simple organic compounds called alpha-hydroxy acids. It was found that when these dry out under warm temperatures, they spontaneously line up into long chains of polyesters.

For the new study, the researchers looked at these reactions under a microscope. They found that these polyester microdroplets were forming gel phases, and when they were wet again they began to form simple structures that resembled cells. The importance of that is that these structures could then compartmentalize biomolecules like nucleic acids and proteins, meaning they could be the first steps to life.

The team found that these structures can stick around for a very long time under the right conditions. Crucially, they can also merge together, something that modern cells can't do. That means they could have collected and shared molecules that reacted to form the earliest genetic and metabolic systems.

Further tests showed just how versatile the microdroplets were as stand-in cells. By exposing them to dyes, the team found that the droplets absorbed outside molecules well. Things like RNA and proteins, which are key to life, were found to still work as catalysts while inside the structures. And lipid layers – which make up the membranes of cells – were found to form on the surface of the droplets.

The researchers can't be sure these specific structures are the direct ancestors of living cells, but showing that the mechanism itself is possible could mean that some similar combination gave rise to protocells.

"This allows us to imagine non-biological systems on early Earth that could still have had a hand in the origins of life," says Tony Jia, lead researcher on the study. "This suggests there may be many other non-biological systems that should be targets of future investigations of this type."

The research was published in the journal PNAS.

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