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We can Build it Better: The First Artificial Cell Network


artificial cells

How does the old saying go? Imitation, is the sincerest form of flattery? Well that is what we’ve been trying to do for a very long time, but mimicking the intricate networks and dynamic interactions that are inherent to living cells is difficult to achieve outside the cell. Unfortunately despite all our intelligence nature has had the upper hand on us for a long time. That has not changed… until now that is.

Scientists have created an artificial, network-like cell system that is capable of reproducing the dynamic behavior of protein synthesis. This achievement is not only likely to help gain a deeper understanding of basic biological processes, but it may, in the future, pave the way toward controlling the synthesis of both naturally-occurring and synthetic proteins for uses we haven’t even thought of yet!

The system itself comprises multiple compartments “etched’’ onto a biochip. These compartments are the artificial cells, each a mere millionth of a meter in depth. They are then connected to one another via thin capillary tubes, creating a network that allows the diffusion of biological substances throughout the system.

Here’s where it get’s really interesting though, within each compartment, the researchers insert a cell genome — strands of DNA designed and controlled by the scientists themselves. Another interesting little trick that the team had to do, in order to translate the genes into proteins, the scientists relinquished control to the bacterium E. coli.

Filling the compartments with E. coli cell extract — a solution containing the entire bacterial protein-translating machinery, minus its DNA code — the scientists were able to sit back and observe the protein synthesis dynamics that emerged.

[Loony Hint: Just because the researchers used E.coli does not mean that they did not have control, nor does it make this any “less cool”. They basically stole the machinery from the E. coli and repurposed it for their use. Without the DNA from the E. coli, the team had full control over what was going on as opposed to letting nature do the work.]

Then, by coding two regulatory genes into the sequence, the scientists created a protein synthesis rate that was periodic. In other words it would “spontaneously” switch from periods of being “on” to “off.” The amount of time each period lasted was determined by the geometry of the compartments [see photo below]. This periodic behavior — a primitive version of cell cycle events — emerged in the system because the synthesized proteins could diffuse out of the compartment through the capillaries, this allowed a mimicking of natural protein turnover behavior in living cells.

At the same time fresh nutrients were continuously replenished, diffusing into the compartment and enabling the protein synthesis reaction to continue indefinitely.

“The artificial cell system, in which we can control the genetic content and protein dilution times, allows us to study the relation between gene network design and the emerging protein dynamics. This is quite difficult to do in a living system,” says Karzbrun.

“The two-gene pattern we designed is a simple example of a cell network, but after proving the concept, we can now move forward to more complicated gene networks. One goal is to eventually design DNA content similar to a real genome that can be placed in the compartments.”


artificial cells

Fluorescent image of DNA (white squares) patterned in circular compartments connected by capillary tubes to the cell-free extract flowing in the channel at bottom. The compartments are 100 micrometers in diameter

The scientists then asked whether the artificial cells actually communicate and interact with one another like real cells. Which, crazy enough, they did communicate. The team found that the synthesized proteins that diffused through the array of interconnected compartments were able to regulate genes and produce new proteins in compartments farther along the network.

In fact, this system resembles the initial stages of morphogenesis — which for those of you who didn’t click the link, is the biological process that governs the emergence of the body plan in embryonic development.

“We observed that when we place a gene in a compartment at the edge of the array, it creates a diminishing protein concentration gradient; other compartments within the array can sense and respond to this gradient.

This is similar to how morphogen concentration gradients diffuse through the cells and tissues of an embryo during early development. We are now working to expand the system and to introduce gene networks that will mimic pattern formation, such as the striped patterns that appear during fly embryogenesis,” explains Tayar.

With the artificial cell system, according to Bar-Ziv, one can, in principle, encode anything:

“Genes are like Lego in which you can mix and match various components to produce different outcomes; you can take a regulatory element from E. coli that naturally controls gene X, and produce a known protein; or you can take the same regulatory element but connect it to gene Y instead to get different functions that do not naturally occur in nature.”

This research may, in the hopefully not too distance future, help advance the synthesis of such things as fuel, pharmaceuticals, chemicals and the production of enzymes for industrial use, just to name a few. I mean imagine being in control of creating anything you could want from biological processes. This could open the door to so many new possibilities it’s even hard to speculate.

Karzbrun E, Tayar AM, Noireaux V, & Bar-Ziv RH (2014). Programmable on-chip DNA compartments as artificial cells. Science (New York, N.Y.), 345 (6198), 829-32 PMID: 25124443


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