Biosensor could lead to new drugs, sensory organs on a chip

Biosensor could lead to new drugs, sensory
organs on a chip

February 7 2023, by Krishna Ramanujan

Graphical abstract. Credit: ACS Synthetic Biology (2023). DOI:
10.1021/acssynbio.2c00531

A synthetic biosensor that mimics properties found in cell membranes
and provides an electronic readout of activity could lead to a better
understanding of cell biology, development of new drugs, and the
creation of sensory organs on a chip capable of detecting chemicals,
similar to how noses and tongues work.

A study, "Cell-Free Synthesis Goes Electric: Dual Optical and Electronic
Biosensor vie Direct Channel Integration into a Supported Membrane

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Electrode," was published Jan. 18 in the journal ACS Synthetic Biology.

The bioengineering feat described in the paper uses synthetic biology to
re-create a cell membrane and its embedded proteins, which are
gatekeepers of cellular functions. A conducting sensing platform allows
for an electronic readout when a protein is activated. Being able to test if
and how a molecule reacts with proteins in a cell membrane could
generate a great many applications.

But embedding membrane proteins into sensors had been notoriously
difficult until the study's authors combined bioelectronic sensors with a
new approach to synthesize proteins.

"This technology really allows us to study these proteins in ways that
would be incredibly challenging, if not impossible, with current
technology," said first author Zachary Manzer, a doctoral student in the
lab of senior author Susan Daniel, the Fred H. Rhodes Professor and
director of the Robert Frederick Smith School of Chemical and
Biomolecular Engineering at Cornell Engineering.

Proteins within cell membranes serve many important functions,
including communicating with the environment, catalyzing chemical
reactions, and moving compounds and ions across the membranes. When
a membrane protein receptor is activated, charged ions move across a
membrane channel, triggering a function in the cell. For example, brain
neurons or muscle cells fire when cues from nerves signal charged
calcium-ion channels to open.

The researchers have created a biosensor that starts with a conducting
polymer, which is soft and easy to work with, on top of a support that
together act as an electric circuit that is monitored by a computer. A
layer of lipid (fat) molecules, which forms the membrane, lies on top of
the polymer, and the proteins of interest are placed within the lipids.

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In this proof of concept, the researchers have created a cell-free
platform that allowed them to synthesize a model protein directly into
this artificial membrane. The system has a dual readout technology built
in. Since the components of the sensor are transparent, researchers can
use optical techniques, such as engineering proteins that fluoresce when
activated, which allows scientists to study the fundamentals via
microscope, and observe what happens to the protein itself during a
cellular process. They can also record electronic activity to see how the
protein is functioning through clever circuit design.

"This really is the first demonstration of leveraging cell-free synthesis of
transmembrane proteins into biosensors," Daniel said. "There's no reason
why we wouldn't be able to express many different kinds of proteins into
this general platform."

Currently, researchers have used proteins grown and extracted from
living cells for similar applications, but given this advance, users won't
have to grow proteins in cells and then harvest and embed them in the
membrane platform. Instead, they can synthesize them directly from
DNA, the basic template for proteins.

"We can bypass the whole process of the cell as the factory that
produces the protein," Daniel said, "and biomanufacture the proteins
ourselves."

With such a system, a drug chemist interested in a particular protein
implicated in a disease might flow potentially therapeutic molecules
across that protein to see how it responds. Or a scientist looking to create
an environmental sensor could place on the platform a particular protein
that is sensitive to a chemical or pollutant, such as those found in lake
water.

"If you think of your nose, or your tongue, every time you smell or taste

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something, ion channels are firing," Manzer said. Scientists may now
                                   take the proteins being activated when we smell something and translate
                                   the results into this electronic system to sense things that might be
                                   undetectable with a chemical sensor."

                                   The new sensor opens the door for pharmacologists to research how to
                                   create non-opioid pain medicines, or drugs to treat Alzheimer's or
                                   Parkinson's disease, which interact with cell membrane proteins.

                                    More information: Zachary A. Manzer et al, Cell-Free Synthesis Goes
                                   Electric: Dual Optical and Electronic Biosensor via Direct Channel
                                   Integration into a Supported Membrane Electrode, ACS Synthetic Biology
                                   (2023). DOI: 10.1021/acssynbio.2c00531

                                   Provided by Cornell University

                                   Citation: Biosensor could lead to new drugs, sensory organs on a chip (2023, February 7)
                                   retrieved 8 March 2023 from https://phys.org/news/2023-02-biosensor-drugs-sensory-chip.html

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