YSM Issue 90.5

structured materials with well-defined physical properties.”
To engineer a genetic circuit in E. coli that produced the pressure
sensor’s scaffolding material, the researchers introduced foreign
plasmids into the bacteria. Plasmids are circular pieces of DNA that
carry a set of instructions telling the bacteria what to do. In this experiment,
the foreign plasmids instructed the bacteria to produce a
protein called curli, which acts as the building block to assemble the
pressure sensor’s dome-like structure.
Following plasmid introduction, the researchers laid out a scaffolding
design with a permeable membrane template—outlined using a
modified inkjet printer—underneath growth media. The membrane
provided structural support for both bacterial growth and the later
addition of gold nanoparticles. After constructing the membrane support,
a liquid culture of the bacteria was applied over the membrane.
Individual bacterial colonies grew into the dome-like shapes, which
researchers could control by adjusting the pore size and hydrophobicity
(the extent of water-repulsion) of the membrane.
To complete the pressure sensor, gold nanoparticles were overlaid
onto the bacterial colony domes after the colonies were fixed into
place. The researchers hypothesized that the viscoelasticity—or resistance
to shear stress and distortion—of the organic curli matrix, combined
with the conductivity of the gold nanoparticles, could contribute
to a functional organic-inorganic hybrid pressure sensor.
Indeed, this is what they observed. When two bacterial domes were
moved to face each other and a constant electrical voltage was applied
to the edge of a dome, the contact between both domes allowed electrical
current to flow. One way to visualize this is by imagining that each
bacterial dome is someone’s face. Just like the spark of a first kiss, when
the two bacterial domes make contact, an electrical current is produced.
Importantly, the strength of the current reflected the strength of the
externally applied pressure. After further testing this relationship, both
verifying and modeling the association, the researchers established that
the bacterial domes could act as robust pressure sensors.
The investigation is a key step toward improving our understanding
of how to program spatial patterns in cell populations, a topic
within synthetic biology that has often been neglected. While this
neglect is partially due to the difficulty of modeling spatiotemporal
patterns over just temporal ones, other concerns include the difficulty
of demonstrating such dynamics experimentally. In this investigation,
the researchers not only addressed such concerns but also took a step
beyond previous work by introducing the programming of self-organization.
Here, the engineered bacteria were able to grow into their
desired structure without any pre-patterning.
What do these bacterial pressure sensors hold for the future? “There
are many opportunities and we’re currently pursuing some of these.
We can imagine the generation of hybrid materials with other properties
that can be used for diverse applications, including environmental
cleanup and medicine,” You said.
Additionally, the researchers discussed the possibility of using curli
to form other structures with different inorganic materials introduced.
For example, if the gold nanoparticles were replaced with catalytic
metal nanoparticles, catalytic structures could be built for many chemical
and physical applications. Likewise, the curli protein itself could
be replaced by other organic molecules to produce materials such as
hydrogels. There is also the possibility of using other organisms, such
as yeast, to create different pattern formations.
The future of this technology holds much promise. “I expect that the
research in this direction will need to simultaneously address two related
►An artist’s rendition of nanoparticles in a cell
cell biology
FEATURE
IMAGE COURTESY OF UNIVERSITY OF TORONTO
issues. One is to push the limit in terms of the diversity of materials that
can be generated by living cells. The other is to generate specific types of
materials for specific applications,” You added. Moving forward, their
team hopes to expand on this work. “As the next step, we’re focusing
on two directions: the generation of different kinds of spatial patterns,
which remains a fundamental challenge in synthetic biology, and the
implementation of different types of hybrid living materials,” You said.
Here at Yale, researchers at the Yale Microbial Sciences Institute are
also employing synthetic biology to make new materials. One such
scientist is Nikhil Malvankar, an assistant professor in the Yale Department
of Molecular Biophysics & Biochemistry. Malvankar’s laboratory
focuses on engineering soil bacteria that produce pili, a naturally conductive,
filamentous protein that functions similarly to copper wires.
His group aims to uncover the mechanisms of electron movement
within these filaments, which act as nanoscale “wires” with tunable
conductivity, to better understand how this system works at the molecular
level and then to apply this knowledge to improve other bacterial
systems. “The long term goals are to use synthetic biology for designing
biomaterials and bioelectronics devices that will complement
and extend current semiconducting technology,” Malvankar said.
Regarding the growing potential of synthetic biology, Malvankar
highlights critical points to consider when working with microorganisms.
“Bacteria are very adaptable organisms and employ multiple
components and redundant pathways for cellular processes.
Furthermore, bacteria can only function in limited environmental
conditions such as physiological pH and aqueous environment,”
Malvankar said. He also provided ideas for improving the bacterial
pressure sensors. “In the future, it should be feasible to use living
cells rather than fixed cells and also avoid expensive and toxic gold
nanoparticles and use all-organic, biological systems.”
With all of these applications and more, the future of synthetic
biology is very exciting. “In the current state of synthetic biology
and bioengineering, one fundamental question is what things we
can actually fabricate using living things. I hope to see different
examples emerging from the community, which can further stimulate
our imagination,” You said.
www.yalescientific.org
December 2017
Yale Scientific Magazine
33