Illinois researchers are the first to count growth factors in single cells



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The nuclei of the bad cancer cells are illuminated (in blue) with quantum dots and the individual EGF growth factors appear as red dots. Credit: Department of Bioengineering of the University of Illinois

Whether healthy or diseased, human cells exhibit behaviors and processes largely dictated by growth factor molecules, which bind to cell receptors. For example, growth factors tell cells to divide, move and die, a process called apoptosis.

When growth factor levels are too high or too low, or cells respond irregularly to their senses, many diseases, including cancer, can result. "Cells are thought to respond to growth factors at extreme levels of sensitivity," said Associate Professor Andrew Smith of the University of Illinois at Bioengineering at Urbana-Champaign. . "For example, a single molecule will cause a major change in cell behavior."

In a recent article published in Nature CommunicationsSmith announced the invention of a new technology platform that numerically counts, for the first time in its history, the amount of growth factor entering an individual cell. Prior to this, the researchers had deduced the growth factor binding as a function of the response of the recipient cells upon introduction of the growth factor molecules.

"We have shown the first direct cause-and-effect relationships of growth factors in individual cells," he said. "We expect the results to lead to a new understanding of cell signaling, cell response to drugs, and resistance of cell populations to drugs, particularly to improve cancer treatments."

Smith's technology platform combines each growth factor with a single fluorescent infrared quantum dot (10 nanometers), which can then be visualized with the help of a three-dimensional microscope. In their study, they counted the number of epidermal growth factor (EGF) molecules linked to predefined human triple-negative bad cancer cells on island-shaped surfaces.

EGF molecules usually signal cell division and lead to tissue growth. Many cancers have mutations in their EGF receptors.

"We used quantum dots as a fluorescent probe because they emit much more light than other conventional fluorescent probes such as organic dyes, and we can adjust their wavelengths by changing their chemical composition," said Phuong Le, PhD student in bioengineering, lead author of the paper. "In our study, we have demonstrated that quantum dots emitting light in the near – infrared wavelength allow for the most accurate counting of cell – binding growth factors.

According to Le, the team also treated bad cancer cells with quantum dot-marked EGF in the absence and the presence of pharmaceutical drugs inhibiting EGF signaling in patients with bad cancer. cells. "We found that the amount of binding to EGF is inversely proportional to the effectiveness of the drug," Le said. "This finding is significant because it means that the signaling molecules present in the tumor of cancer cells – a place where signaling molecules are often poorly regulated – can increase the resistance of cancer cells to pharmaceutical agents."


Explore further:
New quantum dots improve cell imaging

More information:
Phuong Le et al, Growth Factor Counting in Single Cells with Infrared Quantum Dots for Measuring Discrete Pacing Distributions, Nature Communications (2019). DOI: 10.1038 / s41467-019-08754-5

Journal reference:
Nature Communications

Provided by:
University of Illinois at Urbana-Champaign

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