Illuminating tissue formation

Date:
August 4, 2021
Source:
ETH Zurich
Summary:
Researchers have developed a molecule that fluoresces where new
tissue is forming in the body. Alongside helping to detect tumors,
the molecule could play a significant role in research of wound
healing disorders.



FULL STORY ========================================================================== Collagen is the most abundant protein in the human body. It makes up
a third of protein content and single strands assemble to form stable
fibres that give structure to connective tissue such as skin, tendons, cartilage and bones.

Researchers at ETH Zurich have now developed a multi-component molecule
that interacts with collagen and can be used to illuminate new tissue
growth in the body.


==========================================================================
Our bodies start producing more collagen as wounds heal -- or as
tumours grow.

During this process, the fibrous collagen molecules cross-link to create
stable fibres. This requires LOX enzymes, which oxidise certain sites
in the collagen molecules. Subsequently, the chemically altered sites
on different collagen strands react with each other, causing the strands
to fuse together.

Sensor combined with functional peptide Led by Professor Helma Wennemers,
a professor at the Laboratory of Organic Chemistry at ETH Zurich,
the team of researchers developed a sensor molecule with inducible fluorescence. The molecule itself isn't fluorescent, but after reacting
with the LOX enzyme, it begins to light up. In this way, the sensor
molecule acts as a marker for LOX activity. Next, the scientists combined
this molecule with a short fibrous peptide similar to collagen. They
conjugated this peptide with a what is known as a reactive group that
reacts with collagen only if the latter has been oxidised.

In collaboration with researchers from the group led by Sabine Werner, Professor of Cell Biology, the scientists conducted experiments with mice
whose skin had been injected with the multi-component molecule. They also performed in vitro experiments with tissue sections. Their investigations revealed that the molecule anchors itself to collagen fibres where new
tissue is being formed. And it lights up when new tissue starts growing
and the LOX enzyme is being formed. "Thanks to its modular design with
three components -- the sensor, the peptide and the reactive group --
our system is exceptionally specific and precise," says Matthew Aronoff,
senior scientist in Wennemers' group and lead author of the study.

Applications in oncology and wound healing Because new tissue forms
primarily at the edges of tumours as they grow, one application for
the new molecule is in biopsy examinations to show the boundaries of
a tumour. "One of our visions is that surgeons will one day use this
molecule in an operating theatre when removing a tumour," Wennemers says.

The molecule would show surgeons the boundary of the tumour and help
them to remove it entirely.

Other potential applications for the new marker molecule are in the
field of wound healing, for example to investigate tissue formation
in general or healing disorders in patients suffering from diabetes or
other diseases. Such questions are also addressed within the framework
of the interdisciplinary skin research project Skintegrity, in which
ETH Zurich is involved.

Having applied for a patent for their system, the scientists are currently exploring various options for bringing it to market and developing it
for a wider range of applications.

========================================================================== Story Source: Materials provided by ETH_Zurich. Original written by
Fabio Bergamin. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Matthew R. Aronoff, Paul Hiebert, Nina B. Hentzen, Sabine Werner,
Helma
Wennemers. Imaging and targeting LOX-mediated tissue remodeling
with a reactive collagen peptide. Nature Chemical Biology, 2021;
17 (8): 865 DOI: 10.1038/s41589-021-00830-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210804123517.htm

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