The recent discovery of a new phospholipid fills a gap in understanding how primitive cells arose during the origin of life. Approximately 4 billion years ago, conditions suitable for life were created on Earth. Scientists studying the origin of life often wonder whether the type of chemistry found on early Earth was similar to what life requires today. They know that spherical fat accumulations called protocells were the precursors of cells when life first emerged. So how did simple protocells first arise and diversify to eventually lead to life on Earth?

Now, scientists at Scripps Research have identified a plausible pathway for how protocells initially form and progress chemically to provide a variety of functions.

The findings were recently published in the journal Chemicalsuggests that a chemical process called phosphorylation (where phosphate groups are added to a molecule) may have occurred earlier than previously expected. This will lead to the formation of structurally more complex double-stranded protocells that can carry out chemical reactions and share various functions. By figuring out how protocells form, scientists can better understand how early evolution may have occurred.

Building blocks for life

“At some point, we all wonder where we came from. We have now discovered a plausible way that phosphates may be incorporated into cellular structures earlier than previously thought and form the building blocks of life,” said co-author and Scripps Research Professor of Chemistry Ramanarayanan Krishnamurthy. “This discovery helps us better understand the chemical environment of early Earth so we can explore the origins of life and how life may have evolved on early Earth.”

Krishnamurthy and his team are investigating how chemical processes occur that give rise to simple chemicals and structures that existed before the emergence of life on prebiotic Earth. Krishnamurthy is also co-director of a NASA initiative investigating how life emerged in these early environments.

For this study, Krishnamurthy and his team teamed up with soft matter biophysicist Ph.D., co-author and professor in Scripps Research’s Department of Integrative Structural and Computational Biology. Collaborated with Ashok Denis’ laboratory. They tried to investigate whether phosphates played a role in the formation of protocells. Because phosphates are present in nearly every chemical reaction in the body, Krishnamurthy suspected they might be present earlier than previously thought.

Scientists believed that protocells were composed of fatty acids, but it was unclear how protocells switched from a single chain to a double phosphate chain; This allowed them to be more stable and support chemical reactions.

Experimental understanding of the evolution of protocells

Scientists wanted to simulate plausible prebiotic conditions, environments that existed before the emergence of life. For the first time, they identified a mixture of three putative chemicals that could potentially form vesicles, which are spherical lipid structures similar to protocells. The chemicals used included fatty acids and glycerin (a common byproduct of soap making that may have existed on early Earth). They then watched these mixtures react and added additional chemicals to create new mixtures. These solutions were cooled and heated overnight with some shaking to promote chemical reactions.

They then used fluorescent dyes to test the mixtures and determine whether vesicle formation occurred. In some cases, researchers also varied pH and component ratios to better understand how these factors affect vesicle formation. They also looked at the effects of metal ions and temperature on vesicle stability.

“During our experiments, vesicles were able to switch from a fatty acid environment to a phospholipid environment, suggesting that a similar chemical environment may have existed 4 billion years ago,” says first author Sunil Pulletikurthy, a postdoctoral researcher in Krishnamurthy’s laboratory.

It turns out that fatty acids and glycerol may have been phosphorylated to form a more stable double-helix structure. In particular, fatty acid esters derived from glycerol may have given rise to vesicles with different tolerances to metal ions, temperatures, and pH; This is a critical step in diversifying evolution.

“We discovered a possible way phospholipids emerged during this process of chemical evolution,” says Denise. “It is fascinating to learn how early chemistry may have changed to enable life on Earth. Our findings also point to a set of intriguing physical data that may have played an important functional role on the path to modern cells.”

Next, the scientists plan to investigate why some vesicles fuse and others separate to better understand the dynamic processes of protocells.