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May 17, 2005
CELLS' BIOLOGY OVERCOMES THEIR PHYSICAL LIMITATIONS
Working with single-celled amoeba, a team of scientists has found clear evidence that a cell's normal biology sometimes helps it overcome physical laws that would otherwise dictate its behavior during cell division. The findings are published in the May 17 issue of the Proceedings of the National Academy of Sciences.
"Because they are essentially fluid-filled, cells are very much biological and physical systems and subject to the same physical forces that govern the behavior of all fluids," says Doug Robinson, Ph.D., professor of cell biology in the Institute for Basic Biomedical Sciences at the Johns Hopkins School of Medicine.
"We found that, under normal circumstances, the amoeba divide a hundred times slower than if they were a simple fluid, which was a surprisingly large difference," says Robinson. "The cell may have developed its control mechanism to give it more time to reduce errors and limit cell growth."
Robinson and physicist Wendy Zhang, Ph.D., of the University of Chicago, compared how quickly amoeba change shape during cell division (an activity called cytokinesis) to how a similarly shaped sticky fluid like honey would behave. Unlike the cell, honey and other fluids are only subject to the laws of physics.
To get started, Robinson and Zhang, whose expertise is in the physical behavior of fluids, first broke down the amoeba's division into individual steps that could be measured and timed.
For example, the amoeba divide not simply by pinching off through the middle, but by elongating and then forming a barbell-shaped intermediate, which is later cleaved in two. In Robinson's Hopkins lab, the scientists measured the length and width of this "bar" for hundreds of dividing cells, which were magnified by a microscope, and defined the point at which division became inevitable. By comparing normal and genetically engineered amoeba to calculations of the movement of a similarly shaped fluid, the scientists were able to measure the impact of biology.
Scientists know that a fluid's behavior -- whether it stays in a ball-like shape, elongates or splits in two -- is controlled primarily by a physical force called the Laplace pressure. This force, an inherent aspect of the surface of the fluid itself, pushes fluids to ball up, or, if they get too elongated, to break off so they can ball up again.
In the amoeba, the researchers found that in early cell division, the Laplace pressure is pushing the cell to return to a round shape -- that is, not to divide. Once the "bar" is fully formed, however, the Laplace pressure shifts, pushing the cell to split in two and form two round balls.
Surprisingly, the researchers found that the cell's biology counteracts its Laplace pressure at all stages, speeding the earliest steps and slowing the later steps.
"A simple, balled-up fluid wouldn't reach the barbell stage, and if a fluid happened to be barbell-shaped, it would very quickly break into two drops," says Robinson. "But in biology, there's value in carefully controlling this process."
In their experiments, the researchers found that before the bar forms, a centrally located protein called myosin II pushes cell division forward, helping to constrict the center of the cell and enable the barbell shape. Once the barbell shape has been reached, proteins at the cell's periphery -- the outer face of the "weights" -- push against the natural tendency to split in two.
Although the exact impact of the slower-than-possible cell division is unknown, Robinson suggests that it could provide a little extra time for the cell to make sure the DNA and chromosomes are okay before completing cell division, or to redistribute proteins to enable the asymmetric divisions of more complex organisms.
Myosin II, the centrally located protein, and dynacortin, one of the peripherally located proteins that slow division, both have counterparts in human cells, suggesting that the same or a similar system might exist in human cells as well.
Authors on the paper are Zhang and Robinson. The researchers were funded by the Burroughs-Wellcome Fund, the National Institutes of Health and the National Science Foundation.
On the Web:
PNAS 17 May 2005;102(20):7186-7191.