Cancer is one of the leading causes of death globally and this research by ETH Zurich could prove to be significant in detection of tumors and growing clusters of cells. Researchers have created a multi-component chemical that interacts with collagen and can be used to illuminate new tissue formation in the body.
In addition to aiding in the detection of cancers, the molecule could be useful in the study of wound healing diseases. The most abundant protein in the human body is collagen. Single strands assemble to create stable fibres that give structure to connective tissue such as skin, tendons, cartilage, and bones, accounting for a third of protein composition.
As wounds heal—or tumours grow—our bodies begin to produce more collagen. The fibrous collagen molecules cross-link to form stable fibres during this process. This necessitates the use of LOX enzymes, which oxidise specific spots in collagen molecules. The chemically changed locations on distinct collagen strands then react with one another, fusing the strands together.
Image of tumour boundary taken using fluorescence microscopy. The new marker molecule shows the boundary of the tumour in blue; the tumour tissue can be seen above it on the left. Green: collagen, red: cell nuclei.
The research:
The team of researchers, led by Professor Helma Wennemers of ETH Zurich's Laboratory of Organic Chemistry, developed a sensor molecule with inducible fluorescence. This means that the molecule isn't fluorescent on its own, but when it reacts with the LOX enzyme, also called Lipoxygenase enzyme, it starts to glow.
In this way, the sensor molecule serves as a LOX activity marker. Then they linked this molecule with a short fibrous peptide that resembled collagen. A reactive group was attached to this peptide, which reacts with collagen only if it has been oxidised.
In-vitro experiments on tissues revealed that the molecule anchors itself to collagen fibers where new tissue is being formed and it glows as new tissue begins to grow and the LOX enzyme is generated. The modular nature of this technology makes it specific and precise. The three components—the sensor, the peptide, and the reactive group make up this modular system.
Applications:
Because new tissue grows predominantly at the borders of tumours as they grow, the novel molecule could be used in biopsy investigations to show tumour boundaries. One of our aspirations is that surgeons would one day use this molecule in an operating room when removing a tumour. The molecule would indicate surgeons the tumor's boundaries and assist them in completely removing it.
Other possible uses for the novel marker molecule include wound healing research, such as looking into tissue production in general or healing issues in people with diabetes or other conditions. Reference:
Aronoff MR, Hiebert P, Hentzen NB, Werner S, Wennemers H. Imaging and targeting LOX-mediated tissue remodeling with a reactive collagen peptide. Nat Chem Biol. 2021 Aug;17(8):865-871. Doi: 10.1038/s41589-021-00830-6. Epub 2021 Jul 12. PMID: 34253910. | Pubmed
Blog by- Pravajja Vaddikar
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