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Researchers at the University of Illinois, Urbana-Champaign, have developed a new kind of microsensor to answer one of the weightiest questions in biology - the relationship between cell mass and growth rate.
The team, led by Rashid Bashir, published its results in the Proceedings of the National Academy of Sciences. Dr. Bashir is the co-principal investigator of one of six Cancer Nanotechnology Training Centers funded by the National Cancer Institute Alliance for Nanotechnology in Cancer.
Biologists have long questioned whether cells grow at a fixed rate or whether growth accelerates as mass increases. But the mechanics of cellular growth and division are important not only for basic biology, but also for diagnostics, drug development, tissue engineering and understanding cancer. For example, documenting these processes could help identify specific drug targets to slow or stop the uncontrolled growth of cancer cells.
Previous studies have used aggregate populations of cells, making it impossible to determine patterns of individual cell growth. With their small, sensitive microsensors, Dr. Bashir and his colleagues were able to track individual colon cancer cells' masses and divisions over time. The investigators found that the cells they studied did grow faster as they grew heavier, rather than growing at the same rate throughout the cell cycle.
Each microsensor is a tiny, suspended platform made in silicon on a chip. The suspended scale vibrates at a particular frequency, which changes when mass is added. As a cell's mass increases, the sensor's resonant frequency goes down. "As you make the structure smaller and smaller, it becomes more sensitive to the mass that's placed on it," Dr. Bashir said. "A cell is a few nanograms in mass or smaller. If we can make our sensor small enough, then it becomes sensitive to cell mass."
The researchers created an array of hundreds of sensors on a chip. They can culture cells on the chip in much the same way that scientists grow cells in a dish. Thus, they can collect data from many cells at once, while still recording individual cellular measurements. Another advantage of these microsensors is the ability to image cells with microscopes while cells grow on the sensors. Researchers can track the cells visually, opening the possibilities of tracking various cellular processes in conjunction with changes in mass. "Imaging acts as a control. You can actually watch the cell divide and grow and correlate that to your measurements. It really validates what you have," explained Dr. Bashir. "There are lots of optical measurements that now you can integrate with mass sensing."
Next, the researchers plan to extend the study to other cell lines, and explore more optical measurements and fluorescent markers. "These technologies can also be used for diagnostic purposes, or for screening. For example, we could study cell growth and mass and changes in the cell structure based on drugs or chemicals," Bashir said.
This work is detailed in a paper titled, "Measurement of adherent cell mass and growth." An abstract of this paper is available at the journal's website.
View abstract at www.pnas.org/content/107/48/20691
About NCI Alliance for Nanotechnology in Cancer
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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