16/04/10
A team of researchers from the Massachusetts Institute of Technology (MIT) and Harvard University have developed a sensor to weigh individual cells in order to measure the rate at which they accumulate mass. Led by Scott Manalis, associate professor of biological engineering at MIT, the team sought to discover whether cells grow exponentially or linearly because previous studies have yielded conflicting data. Previous measurement techniques have focused on a cell’s volume or length instead of mass, which limited the precision necessary for single cell growth studies. Now, researchers have successfully measured the accumulation of mass in single cells to determine that cells grow exponentially.
Biosensor reveals that cells grow exponentially
04/16/2010
Erin Podolak
Researchers have measured the rate at which single cells accumulate mass to help explain how cells control their growth.
Scientists have held a firm understanding of the cell division process for years, however, “the problem of cell growth—how a cell regulates the amount of material it makes—is not well known at all,” Marc Kirschner, professor of systems biology at Harvard Medical School, said in a press release. To provide a better understanding of the relationship between cell growth and cell division, the research team developed a new biosensor—described in a recent paper in Nature Methods—to measure a cell’s mass as it accumulates.“Over the two-fold size range experienced by most proliferating cells, linear and exponential growth curves differ by less than 10 percent,” said Manalis, a member of MIT’s David H. Koch Institute for Integrative Cancer Research. “So the measurement precision must be much less than this.”
The researchers used a cell-mass sensor first demonstrated by Manalis in 2007 to measure cells’ mass as they grow over a given time period, ranging from 5 to 30 minutes. The sensor consists of a fluid-filled microchannel etched on a tiny silicon slab that vibrates inside a vacuum. Cells are flowed through the channel one at a time, and their mass slightly alters the slab’s vibration frequency. The mass of the cell is calculated by this change in vibration frequency, with a resolution as low as a femtogram. By coordinating the flow direction, the researchers were able to trap a cell within the microchannel so that the cell could be repeatedly passed through the channel every few seconds, and its mass recorded each time it passed through.
Four types of cells were used for this study: Escherichia coli, Bacillus subtilis, Saccharomyces cerevisae, and mammalian lymphoblasts. The results indicated that B. subtilis, S. cerevisae, and the mammalian lymphoblast cells appear to grow exponentially; however, results for E. coli were inconclusive because of high levels of variation between individual E. coli cell growth rates, the team wrote.
If cells grow exponentially, the researchers believe there must be a control mechanism. Otherwise, when cells divide into daughter cells of slightly different sizes, the larger cell in each division would always growth faster than the smaller one. "If there were no control over the process, the variation in cell size would be all over the map," said Kirschner. Because this is not the case, the researchers intend to investigate how this control mechanism may function.
The researchers are now working to tag proteins inside the cells with fluorescent molecules to help determine when in the cell cycle cells have the most mass. According to Manalis, understanding the mechanism that controls cell growth may shed light on diseases that are caused by abnormal cell growth, like cancer, so the researchers also intend to develop ways to add chemical nutrients, antibiotics, and cancer fighting drugs to the fluid in the microchannel to determine how these substances affect growth rates.
The paper, "Using buoyant mass to measure the growth of single cells," was published April 11 in Nature Methods.
E. Coli cells. Source: Wikipedia Commons.