In a process that is shrouded in mystery, rod-shaped bacteria
reproduce by splitting
themselves in two. By applying advanced mathematics to laboratory
data, a team led by Johns Hopkins
researchers has solved a small but important part of this
The findings apply to highly common rod-shaped bacteria such as
E. coli, found in the human
digestive tract. When these single-celled microbes set out to
multiply, a signal from an unknown
source causes a little-understood structure called a Z-ring to
tighten like a rubber band around each
bacterium's midsection. The Z-ring pinches the rodlike body into two
microbial sausages that finally
split apart. To shed light on this process, the Johns Hopkins–led
team developed a mathematical tool
that computed the mechanical force exerted by the Z-ring when it
helps these cells split.
The calculation will aid scientists who are trying to learn more
about how these microbes live
and reproduce. The work also may hasten the development of a new type
of antibiotic that could
disable the Z-ring to keep harmful bacteria in check.
The bacteria research was reported in the Oct. 9 edition of
Proceedings of the National
Academy of Sciences. The work was led by Sean X. Sun, an
assistant professor of mechanical
engineering in Johns Hopkins' Whiting School of Engineering.
"This type of bacteria is commonly found in the human body,"
said Sun, a co-author of the
journal article. "Understanding how organisms like this work can help
us find new ways to treat
bacterial illnesses, develop medications or do any type of
bioengineering involving bacteria. If you want
to target certain cellular activities, you need to know how
single-celled creatures like this operate."
Sun's team brought a fresh perspective to the study of cell
activity. While traditional biologists
try to identify and learn the function of tiny bits of genetic
material within cells, Sun studies how
such proteins work together to form "molecular machines" that carry
out tasks inside the cells.
"Biologists are just beginning to understand that mechanical
processes at the cellular level are also
important," he said. "I'm bringing the tools of mechanical
engineering to bear on biological mysteries."
Toward this goal, Sun's team's sought to measure how much
mechanical force the Z-ring applies
to rod-shaped bacteria during cell division. The researchers knew
that each rod-shaped bacterium
possesses, around the inside of its midsection, a belt made of a
filamentous protein called FtsZ. Most
of the time, this ring is inactive. But when a bacterium cell is
healthy and has sufficient food, it seeks
to reproduce by dividing in two. When it is time for this to occur,
the Z-ring receives a signal and
begins to contract. This pinching continues until the rod breaks
apart to form two daughter cells.
Sun's team gathered data from microbiology labs that are
studying cell division and then
translated these observations into mathematical equations. The
researchers used the equations to
create computer simulations of the cell division process, models that
yielded a prediction of the Z-ring
force: 8 piconewtons. A piconewton is one-trillionth of a newton,
which is approximately the amount of
force needed to lift a baseball in Earth's gravity.
"The surprise was that the amount of force generated by the
Z-ring was so small," Sun said.
"Most researchers believed a lot more force would be required during
the cell division process."
This information could be used, Sun said, by drug developers
seeking a way to disable the Z-ring
so that harmful bacteria can no longer reproduce. The research has
wider implications as well. "Our
mathematical equations could also be used to help understand how
plant and animal cells divide,
including human cells," Sun said. "Human cells have an actin ring
that behaves the same way as a Z-ring.
It contracts during division. The mathematical formulas developed in
this study could also be used in
research concerning the division of human cells. The more we know
about this process, the better we
can affect the process through drugs or genetic manipulation."
The lead author on the PNAS article was Ganhui Lan, a doctoral
student supervised by Sun. The
other co-author was Charles Wolgemuth, an assistant professor in the
Department of Cell Biology and
the Center for Cell Analysis and Modeling at the University of
Connecticut Health Center in
Sun also is affiliated with the Institute for NanoBioTechnology
at Johns Hopkins. His team's
research was supported by funding from the National Institutes of