Scientists say they think they have discovered the mechanism that drives a rapidly-growing cell to divide into two smaller cells. They published their study “Cell-Size Control and Homeostasis in Bacteria” in Current Biology. And their finding is not what many biologists expected.

“How cells control their size and maintain stable size distributions is one of the most fundamental, unsolved problems in biology,” said Suckjoon Jun, Ph.D., an assistant professor of physics and molecular biology at UC San Diego, who headed the research study with Massimo Vergassola, Ph.D., a professor of physics. “Even for the bacterium E. coli, arguably the most extensively studied organism to date, no one has been able to answer this question.”

Finding a solution was more than a basic-science pursuit for the scientists, who pointed out that learning more about the triggers of cell division would enable researchers to better understand such processes as the runaway cell division that leads to cancer. To conduct the study, Dr. Jun and his colleagues developed a tiny device to isolate and physically manipulate individual genetic materials.

“It turned out that we can use this device to also follow the life history of thousands of individual bacterial cells for hundreds of generations,” he said. “We looked at the growth patterns of the cells very, very carefully, and realized that there is something really special about the way the cells control their size.

“In our study, we monitored the growth and division of hundreds of thousands of two kinds of bacterial cells, E. coli and B. subtilis, under a wide range of tightly controlled steady-state growth conditions. This produced statistical samples about three orders of magnitude, or a thousand times better, than those previously available. We could thus pursue an unprecedented level of quantitative analysis.”

The scientists found through their development of mathematical models that matched their experimental data that the growth of cells followed the growth law, essentially exponential growth based on a constant rate. But they also found to their surprise that cell size or the time between cell divisions had little to do with when the cells divided. Instead, to keep the distribution of different sized cells within a population constant, the cells followed what the researchers termed “an extraordinarily simple quantitative principle of cell-size control.”

“Our combined experimental results and quantitative analysis demonstrate that cells add a constant volume each generation, irrespective of their newborn sizes, conclusively supporting the so-called constant Δ model,” wrote the investigators. “This model was introduced for E. coli and recently revisited, but experimental evidence was limited to correlations. This “adder” principle quantitatively explains experimental data at both the population and single-cell levels, including the origin and the hierarchy of variability in the size-control mechanisms and how cells maintain size homeostasis.”

“Specifically, we showed that cells sense neither space nor time, but add constant size irrespective of their birth size,” explained Dr. Jun. “This 'adder' principle automatically ensures stability of size distributions.

E. coli and B. subtilis are one billion years divergent in evolution, and they are the textbook examples of the diversity of molecular details for biological controls in different bacterial species. Thus, their sharing the same quantitative principle for size maintenance is a textbook level discovery.”

In addition to UC San Diego, other universities involved in the research were the City University of New York, UC Berkeley, Washington University, and Harvard Medical School.

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