Researchers from Duke University have turned bacteria into builders of useful devices by programming them with a synthetic gene circuit.
As a bacterial colony grows into the shape of a hemisphere, the gene circuit triggers the production of a protein to distribute within the colony that can recruit inorganic materials. When supplied with gold nanoparticles by researchers, the system forms a golden shell around the bacterial colony, the size and shape of which can be controlled by altering the growth environment.
A demonstration of the pressure sensor built by bacteria in action as a researcher taps out some Morse code. (Will (Yangxiaolu) Cao, Kara Manke, Duke University)
The result is a device that can be used as a pressure sensor, providing that the process can create working devices.
While other experiments have been successful in growing materials using bacterial processes, they relied entirely on externally controlling where the bacteria grow and have been limited to two dimensions. In the study, Duke researchers demonstrate the production of a composite structure by programming the cells themselves and controlling their access to nutrients, but still leaving bacteria free to grow in 3D.
"This technology allows us to grow a functional device from a single cell," said Lingchong You, associate professor of engineering at Duke. "Fundamentally, it is no different from programming a cell to grow an entire tree."
Nature has many examples of life combining organic and inorganic compounds to make better materials. Mollusks grow shells consisting of calcium carbonate interlaced with a few organic components, resulting in microstructure three times tougher than calcium carbonate alone. Our bones are a mix of organic collagen and inorganic minerals made of various salts.
Harnessing construction abilities in bacteria would have many advantages over current manufacturing processes. In nature, biological fabrication uses raw materials and energy efficiently. In the synthetic system tweaking growth instructions to create different shapes and patterns could theoretically be cheaper and faster than casting the new dies or molds needed for traditionally manufacturing.
"Nature is a master of fabricating structured materials consisting of living and non-living components," said You. "But it is extraordinarily difficult to program nature to create self-organized patterns. This work, however, is a proof-of-principle that it is not impossible."
The genetic circuit is like a biological package of instructions that researchers embed into a bacterium's DNA. The directions tell the bacteria to produce a protein called T7 RNA polymerase (T7RNAP), which activates its own expression in a positive feedback loop. It produces a small molecule called AHL that can diffuse into the environment like a messenger.
As the cells multiply and grow, the concentration of the small messenger molecule hits a critical concentration threshold, which triggers the production of two more proteins called T7 lysozyme in curli. The former inhibits the production of T7RNAP while the latter acts like a biological Velcro that can latch onto inorganic compounds.
The dynamic interaction of these feedback loops causes the bacterial colony to grow in a dome-shaped pattern until it runs out of food. It causes the bacteria on the outside of the dome to produce the biological Velcro, which grabs onto gold nanoparticles supplied by the researchers, which forms a shell about the size of your average freckle.
The researchers could alter the size and shape of the dome by controlling the properties of the porous membrane it grows on. For example, changing the size of the pore or how much the membrane repels water affects how many nutrients are passed to the cells, altering their growth pattern.
"We're demonstrating one way of fabricating a 3-D structure based entirely on the principle of self-organization," said Stefan Zauscher, professor of mechanical engineering & materials science at Duke. "That 3-D structure is then used as a scaffold to generate a device with well-defined physical properties. This approach is inspired by nature, and because nature doesn't do this on its own, we've manipulated nature to do it for us."
To show how their system could be used to manufacture the working device, the researchers used these hybrid organic/inorganic structures as pressure sensors. Identical arrays of domes were grown on two substrate surfaces. The two substrates were sandwiched together so that each dome was positioned across from its counterpart on the other substrate.
Each dome was connected to an LED light bulb through copper wiring. When the pressure was applied to the sandwich, the domes pressed onto one another, causing a deformation that results in an increase in its conductivity. This caused the corresponding LED light bulbs to brighten a certain amount depending on the amount of pressure being applied.
"In this experiment, we're primarily focused on the pressure sensors, but the number of directions this could be taken in is vast," said Will (Yangxiaolu) Cao, a postdoctoral associate in You's laboratory and first author of the paper. "We could use biologically responsive materials to create living circuits. Or if we could keep the bacteria alive, you could imagine making materials that could heal themselves and respond to environmental changes."
"Another aspect we're interested in pursuing is how to generate much more complex patterns," said You. "Bacteria can create complex branching patterns, we just don't know how to make them do that ourselves -- yet."
A paper on this study was published on October 9th in Nature Biotechnology.
