Capsule in the wear track.

Telephoning
is a mutual exchange of information: A phones B and they both agree
what B should do. Once this is done, Party B phones Party A to let him
or her know. A no longer phones B. During this two-way communication,
electrical signals are sent, and for their transmission suitable devices
are necessary.

Based
on this formula, a team of bioengineers headed by Martin Fussenegger
and Jörg Stelling at ETH Zurich’s Department of Biosystems Science and
Engineering in Basel has programmed mammalian cells in such a way that
two cells can communicate via chemical signals. The scientists have thus
incorporated a synthetic two-way communication system into mammalian
cells for the first time that also responds to concentration differences
in the signal molecules. The researchers used suitable signal molecules
and constructed “devices” out of biological components that receive,
process and respond accordingly to the signals. The devices consist of
suitable genes and their products, proteins, which are linked to each
other logically.

System switches itself off

An
enzyme produces the amino acid L-tryptophan from indole, which has been
introduced into the sender cell from outside. This little molecule
enters the receiver cell, which processes the signal. The response to
L-tryptophan is that the receiver produces acetaldehyde, which the
sender cell can receive. If, after a certain time, a particular
concentration of acetaldehyde has been attained or the indole is
depleted, the sender cell stops producing L-tryptophan and the system
switches itself off again.

“This
systematic communication network is quite literally a ‘cell phone’,”
says Martin Fussenegger. Although other scientists have already
developed synthetic communication networks for bacteria and yeast cells,
theirs is the first for mammalian cells as this cell type is far more
complex.

Modules can be reconnected

For
their experiment, the Basel-based researchers used so-called HEK cells –
human kidney cells, in other words, which are often used in research.
Moreover, the biological components necessary to construct the signal
network can be used in a modular way. With these modules, the
researchers were also able to connect other signal paths, including a
signal cascade leading from the sender cell, through the information
processing cell to the performing receiver cell without any feedback.

Two-way
communication between different cell types is important in
multicellular organisms. It regulates inflammatory responses, the
development of extremities like hands and feet, controls the body’s
blood sugar level via insulin and glucagon, and controls the development
and maintenance of the vascular system.

Network controls blood-vessel formation

Thanks
to their “cell phone”, the ETH-Zurich biotechnologists were able to
simulate the latter accurately in a cell culture. They placed the sender
and receiver module in the culture dish along with a population of
endothelial cells, which line the blood-vessel walls. In response to the
tryptophan signal, the receiver module formed the messenger VEGF as
well as acetaldehyde. This increases the permeability of the endothelial
cells, which is a key prerequisite for blood-vessel growth.

Due
to the acetaldehyde response, the sender module ultimately produced the
signal molecule Ang1, which stops the permeability of the endothelial
cells to inhibit blood-vessel growth.

This
signal system is also found in the human body. If VEGF spirals out of
control, however, too many blood vessels form, which ultimately feeds a
growing tumour. The “cell phone” could therefore be a plausible strategy
to halt the pathological formation of new blood vessels.

“Communication
is extremely important in controlling blood vessels,” says Fussenegger,
“and we hope to be able to use synthetic ‘cell phones’ to correct or
even cure disease-related cell communication systems precisely in the
future with a ‘therapeutic call’.”

Synthetic two-way communication between mammalian cells

Source: ETH Zurich