Issue Date: June 9, 2008
Membranes By Design
The advent of synthetic life may have gotten a bit closer. Biochemist Jack W. Szostak and colleagues at Massachusetts General Hospital have designed a fatty acid container that takes in building blocks from outside to supply a spontaneous DNA-copying reaction on the inside (Nature, DOI: 10.1038/nature07018).
The synthetic biology advance, Szostak says, suggests a way by which primitive cells could have obtained nutrients, a key unknown in the origin-of-life field. It's not clear whether the earliest cells made their own components or incorporated them from outside, he says.
Modern cell membranes are barricades that require protein pumps and pores for shuttling nutrients in and out. But early membranes might not have behaved in the same way, Szostak says.
His team has now used a mixture of fatty acids, fatty alcohols, and esters to make a synthetic barrier that is more permeable to sugars and nucleotides than today's biological membranes. "Our experiments show that primitive cells may well have been able to absorb nutrients from their environment," he says.
The team formed membranes with optimized mixtures of amphiphiles, molecules with polar heads and nonpolar tails. These membranes allow small molecules to enter the volume they enclose but don't permit polymers inside to leak out.
The researchers found that modified versions of conventional membrane components—such as lipids with shorter fatty acid chain lengths and larger head groups—improved the permeability of their synthetic membranes. By adding lipids with these properties—such as glycerol monodecanoate—to a mixture of amphiphiles, they made membranes that were more permeable to ribose, the sugar component of RNA, as well as to nucleotides.
Szostak's group then encapsulated a synthetic DNA molecule in their primitive membranes. They had previously found that this particular DNA, if given access to activated nucleotides, could guide production of complementary DNA without enzymes. Sure enough, the synthetic membrane let nucleotides in where they assembled into the complementary DNA product, which then remained in the primitive cell.
"This work beautifully weaves together two of the central themes of life's origins: the emergence of replicable genetic polymers and the advantage of compartmentalization in sequestering the fruits of metabolic labor," says Gerald F. Joyce of the Scripps Research Institute, who studies self-replicating RNA.
Despite having demonstrated a specific DNA-copying reaction, Szostak notes that "the chemistry of nucleic acid replication is the remaining hard part" of making a fully synthetic cell. He and his coworkers are now working on making the nucleotide chemistry used in the current study more generally applicable.
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