Illinois researchers are the first to calculate growth factors in individual cells

Whether healthy or diseased, human cells exhibit behaviors and processes that are highly dictated by growth factor molecules that bind to receptors in the cells. For example, growth factors tell cells to divide, move and when to die – a process known as apoptosis.

When the growth factor levels are too high or too low or when the cells respond irregularly to their instructions, many diseases can occur, including cancer. "It is believed that cells respond to growth factors at extreme sensitivity levels," said Professor Andrew Smith of the University of Illinois at Urbana-Champaign Bioengineering. "For example, a single molecule will result in a significant change in cell behavior."

In a recent publication on Nature Communications, Smith referred to the invention of a new technology platform that digitally measures for the first time the amount of growth factor entering a single cell. Prior to this, the researchers concluded that the growth factor binding was based on how the recipient cells responded when the growth factor molecules were introduced.

"We have shown the first direct cause-effect relationships of growth factors in individual cells," he said. "We expect the results to lead to a new understanding of cell signaling, how cells respond to drugs, and why cell populations become drug-resistant, especially to improve cancer therapies."

The Smith Technology Platform identifies each growth factor with a unique mechanical (10 nanometers) infrared fluorescent quantum dot, which can then be projected using a three-dimensional microscope. In their study, they measured how many epidermal growth factor (EGF) molecules bound to human triple-negative breast cancer cells that had been preformed on island-like surfaces.

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

"We used quantum dots as fluorescent probes because they emit much more light than other conventional fluorescence detectors like organic pigments and we can resonate their wavelengths by changing their chemical composition," said Phi Phong Le, of the paper. "In our study, we have demonstrated that quantum dots emitting light to the near infrared wavelength have allowed more accurate measurement of cell-mediated growth factors."

According to Le, the group also treated breast cancer cells with EGF with quantum dot in the absence and presence of drug drugs that inhibit EGF signaling in cells. "We found that the amount of EGF binding is inversely related to drug efficacy," Le said. "This finding is important as it means that the signaling molecules present in the tumor cell tumor – a place where signaling molecules are often not properly regulated – can enhance the resistance of cancer cells to pharmaceutical agents."

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Apart from Smith and Le, other researchers involved in this study include Illinois Physics Professor Hee Jung Chung and postgraduate student Brian Baculis, who has conducted confirmatory studies of molecular biology. former researcher of Illinois, Sung Jun Lim, who performed quantum artificial synthesis. and Professor Kristopher Kilian of the University of New South Wales, who designed the micro-contact printing process for cellular islands.

This project was funded by the National Institutes of Health and the University of Illinois at Urbana-Champaign.

Recently, Assistant Professor Smith and Bioengineering Pablo Perez-Pinera received more than $ 1 million from funding from the National Institutes of Health to further expand Smith's new technology with new engineering tools and image analysis software. The aim of the R01 grant will be to develop a quantitative analysis platform for signaling a cell via growth factors and cytokines.