Synthetic biology—our attempt to engineer living organisms—has put a lot of effort into making genetic circuitry mimic what we do in silicon. Logical gates, amplifiers, and more have all been implemented using DNA and proteins. While these feats of genetic engineering have been impressive, how we’d put these genetic circuits to use hasn’t always been clear. It’s easy to imagine a logical gate in a bacteria would be useful for various biotechnology applications, but there haven’t been many opportunities when someone put one to use.
An exception to this was reported in this week’s edition of Nature Biotechnology. A team at Duke University has engineered a bacterial population that uses engineered genetic circuitry to express a protein only in specific locations. The researchers then printed these bacteria onto a surface and processed them to coat the protein in gold. The result is a tiny gold dome that makes a great pressure sensor.
The circuit itself is interesting in its own right. One part of it is pretty simple: a gene encodes a protein that feeds back to the gene itself, making sure it’s active. Thus, once this gene becomes activated, it stays activated unless something else happens.
The same protein, however, also activates a second set of genes. One of these produces a small chemical that can diffuse between bacteria, carrying a signal among them. The second gene encodes a protein that binds this chemical signal. When the protein and signal are together, they can activate other genes. Now, three genes removed from where we started, the researchers engineered one that responded to the chemical signal by producing a protein that destroyed the first.
Overall, this creates a giant negative feedback loop—if the first gene is active, it should lead to the protein it makes being destroyed, which shuts the gene back down. But there’s a twist to this, thanks to the chemical that’s in the middle of the loop. If only a single cell is making the chemical, it’ll diffuse away and the loop won’t go to completion. Instead, you need neighboring cells producing it, too, for the chemical to reach levels where it leads to gene activation. Thus, the whole loop becomes sensitive to whether there are enough other engineered cells around.
When the full loop is active, however, one of the genes that gets turned on encodes a protein that forms a structure outside the bacteria. Thus, the production of the structure becomes sensitive to the number of engineered cells around.
Engineered cells meet engineering
All that may seem complicated, but the researchers were just getting started. To get the bacteria to make a structure in the desired pattern, they used an inkjet printer to make a pattern of bacteria on a membrane. That membrane was then placed on a source of nutrients, allowing the bacteria to grow into colonies. The size and shape of the colonies could be controlled by using membranes with different pore sizes, which let different amounts of nutrients through. (All of the colonies grew into rounded, button-like shapes, but the precise height and width depended on the membrane.)
Looking at these colonies, the researchers found that the structure made by their engineered bacteria tended to be on the periphery. Very little was made on the interior of the colony, presumably because the chemical was present at high enough levels to shut the whole system down. The result was a tiny dome-like structure sitting on the membrane.
To convert this into electronics, the team obtained some antibodies to the protein that had formed the dome and linked them up to gold nanoparticles. After immobilizing the proteins, the researchers let the antibodies stick to the dome, converting it to a gold-rich surface.
To turn this into hardware, they made two identical membranes and placed them opposite each other, held apart by a flexible gasket. When pressure was applied to the membranes, the gold domes made contact, creating a circuit. Thus, the presence of current would indicate that pressure had been sensed. The amount of current went up as the pressure increased and as more of the gold came in contact as the domes were smushed into each other.
The researchers went on to show that, by controlling the flow of nutrients while the bacteria were growing, they could make hardware with different sensitivity to pressure. By hooking them up in series, it was also possible to create a bacterial “track pad,” able to sense where fingers had been pushed against the surface.
Overall, the system seems full of potential. Since the bacteria can be printed in lines and other shapes, there’s no reason for the structures made this way to be limited to domes. And we can link all sorts of things to antibodies, so we can think well beyond metals when it comes to the sorts of things we build with bacteria.
The only real question is whether this technology offers any advantage over traditional manufacturing techniques, which can typically knock out thousands of customized parts in the time it takes bacteria to undergo a couple of cell divisions. The real advantage that this system seems to have is that it can mix traditional materials with some of the complicated chemistry that’s hard to do anywhere other than a biological system. Figuring out how we might use that capability, for the moment, is left as an exercise for the reader.