Study Reveals How Simple Molecules Could Have Formed Early Cell Membranes

Few questions have captivated humankind more than the origin of life on Earth. How did the first living cells come to exist? How did these early protocells develop the structural membranes necessary for cells to thrive and assemble into complex organisms?

New research from the lab of University of California San Diego Professor of Chemistry and Biochemistry Neal Devaraj has uncovered a plausible explanation involving the reaction between two simple molecules. This work appears in Nature Chemistry.

Life on Earth requires lipid membranes – the structure of a cell that houses its interior mechanics and acts as a scaffold for many biological reactions. Lipids are made from long chains of fatty acids, but before the existence of complex life, how did these first cell membranes form from the simple molecules present on Earth billions of years ago?

Scientists believe that simple molecules of short fatty chains of fewer than 10 carbon-carbon bonds (complex fatty chains can have nearly twice that many bonds) were abundant on early Earth. However, molecules with longer chain lengths are necessary to form vesicles, the compartments that house a cell's complicated machinery.

While it may have been possible for some simple fatty molecules to form lipid compartments on their own, the molecules would be needed in very high concentrations that likely did not exist on a prebiotic Earth – a time when conditions on Earth may have been hospitable to life but none yet existed.

"On the surface, it may not seem novel because lipid production happens in the presence of enzymes all the time," stated Devaraj, who is also the Murray Goodman Endowed Chair in Chemistry and Biochemistry. "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 uncover an explanation for these first lipid membranes, Devaraj's team started with two simple molecules: an amino acid named cysteine and a short-chain choline thioester, similar to molecules involved in the biochemical formation and degradation of fatty acids.

The researchers used silica glass as a mineral catalyst because the negatively charged silica was attracted to the positively charged thioester. On the silica surface, the cysteine and thioesters spontaneously reacted to form lipids, generating protocell-like membrane vesicles stable enough to sustain biochemical reactions. This happened at lower concentrations than what would be needed in the absence of a 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? Here we have provided one possible explanation of what could have happened."

Neal Devaraj, Professor of Chemistry and Biochemistry, University of California San Diego

Full list of authors: Christy J. Cho, Taeyang An, Alessandro Fracassi, Roberto J. Brea and Neal K. Devaraj (all UC San Diego); Yei-Chen Lai, Alberto Vázquez-Salazar and Irene A. Chen (all UCLA).

This research was supported, in part, by National Science Foundation (EF-1935372) and the National Institutes of Health (R35-GM141939).