All known life forms are made up of cells enclosed by lipid membranes that separate and protect the cell’s contents. The exact way the first life forms were compartmentalized remains unclear. Some models propose that single-chain lipids, like fatty acids, played a role in this process. However, membranes made from shorter alkyl chains (≤C8), which may have been more common on early Earth, tend to be unstable.
New research from Professor Neal Devaraj’s lab at UC San Diego suggests a possible solution to the mystery of how early life forms were compartmentalized. Scientists believe short fatty acid chains (with fewer than ten carbon-carbon bonds) were abundant on prebiotic Earth. Still, longer chains are needed to form stable vesicles, essential for creating cell-like compartments.
While some simple fatty molecules might have formed lipid compartments, they would have required very high concentrations that were likely absent on early Earth, a time when life had not yet emerged.
University of California San Diego Professor of Chemistry and Biochemistry Neal Devaraj said, “On the surface, it may not seem novel because lipid production happens in the presence of enzymes all the time. But over four billion years ago, there were no enzymes. Yet, somehow, these first protocell structures were formed. How? That’s the question we were trying to answer.”
To investigate how the first lipid membranes might have formed, Devaraj’s team began with two simple molecules: cysteine, an amino acid, and a short-chain choline thioester, similar to molecules involved in fatty acid metabolism.
The researchers used silica glass as a catalyst, taking advantage of its negatively charged surface, which attracted the positively charged thioester. On the silica surface, cysteine and thioester molecules spontaneously reacted to form lipids, creating protocell-like membrane vesicles.
These vesicles were stable enough to support biochemical reactions and could form at lower concentrations than possible without the silica catalyst.
“Part of the work we’re doing is trying to understand how life can emerge in the absence of life. How did that matter-to-life transition initially occur?” said Devaraj. “Here, we have provided one possible explanation of what could have happened.”
Journal Reference:
- Cho, C.J., An, T., Lai, YC. et al. Protocells by spontaneous reaction of cysteine with short-chain thioesters. Nat. Chem. (2024). DOI: 10.1038/s41557-024-01666-y
