BioEd Online

Primitive cells similar to bacteria have been created by US researchers. These synthetic cells are not truly alive, because they cannot replicate or evolve. But they can churn out proteins for days, and could be useful for drug production, as well as advancing the quest to build artificial life from scratch.

Vincent Noireaux and Albert Libchaber of the Rockefeller University in New York have managed to package up some of the molecular machinery of a cell inside an artificial, bacterium-sized membrane. And they can perforate the membrane with holes that allow nutrients and energy-rich molecules to get into the cells from the surroundings.

These protocells contain all the machinery needed to generate proteins from their raw ingredients (amino acids), so they could be used as miniature factories, to produce proteins of industrial and medical value.

Such proteins, for example, insulin, are routinely produced by genetically engineered bacteria bred in fermentation vats. But artificial cells would make much simpler protein factories, perhaps more easily tailored to make specific products.

Mixing it up

Ready-made mixtures of all the biomolecules that a cell needs for protein production are commercially available, extracted from bacteria such as Escherichia coli. These mixtures can make specific proteins, but they stop working within about two hours unless they are continually fed with raw materials and cleaned of waste products.

To enclose this biomolecule mixture inside membranes like those of natural cell walls, Noireaux and Libchaber made microscopic droplets of the cell extract suspended in oil. Soap-like molecules called phospholipids then coated the surface of these droplets in the same way that emulsifying agents surround the droplets in a salad dressing, stopping them from coalescing.

The researchers then coated the droplets with a second layer of phospholipids, to form a double layer that looks just like the membrane of a real cell. They publish their results in the Proceedings of the National Academy of Sciences¹.

To monitor the behaviour of their cells, Noireaux and Libchaber added DNA that encodes a fluorescent protein, so that as the cells produce it, they start to glow. Whereas the bare cell extract ran out of steam after two hours, wrapping the molecules in a membrane kept the system 'alive' for more than twice as long.

To get raw materials into the protocells from the surroundings, the researchers added a bacterial gene that encodes a protein called alpha-hemolysin. This protein has a hollow, barrel-shaped structure and it inserts itself into cell membranes to create pores. Once fitted with these molecular portals, the cells kept churning out the fluorescent protein for days.

Right track

The work is very clever, according to David Deamer, a chemist at the University of California, Santa Cruz, who has also tried to devise artificial protocells. "These guys are on the right track," he says. "It's a big step forward."

Noireaux and Libchaber are now working on fixing molecules to their protocell walls that will pinch the membranes together so that the cells can divide, as bacteria do. This could be the first step in making artificial cells that replicate.

Deamer says getting the cells to divide would be "spectacular", but adds that another big challenge is to enable the transcription and translation apparatus to make copies of itself, so that the new cells can both function like their 'parent'.