• Biosensor could lead to new drugs, senso

    From ScienceDaily@1:317/3 to All on Tue Feb 7 21:30:30 2023
    Biosensor could lead to new drugs, sensory organs on a chip

    Date:
    February 7, 2023
    Source:
    Cornell University
    Summary:
    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.


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    FULL STORY ==========================================================================
    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
    Electrode," was published Jan. 18 in the Synthetic Biology journal of
    the American Chemical Society.

    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.

    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 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.

    Surajit Ghosh, a postdoctoral researcher in Daniel's lab, is a co-first
    author.

    Neha Kamat, assistant professor of biomedical engineering at Northwestern University, is a senior co-author of the paper.

    The study was funded by the National Science Foundation, the Air Force
    Office of Scientific Research, the American Heart Association, the
    National Institute of General Medical Sciences and the Defense Advanced Research Projects Agency.

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    ========================================================================== Story Source: Materials provided by Cornell_University. Original written
    by Krishna Ramanujan, courtesy of the Cornell Chronicle. Note: Content
    may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Zachary A. Manzer, Surajit Ghosh, Arpita Roy, Miranda L. Jacobs,
    Juliana
    Carten, Neha P. Kamat, Susan Daniel. 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 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2023/02/230207191600.htm

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