James E.
Kloeppel, Physical Sciences Editor
217-244-1073; kloeppel@illinois.edu
4/7/2005
CHAMPAIGN, Ill. —
Researchers using an extremely fast and accurate imaging technique have
shed light on the tiny movements of molecular motors that shuttle material
within living cells. The motors cooperate in a delicate choreography
of steps, rather than engaging in the brute-force tug of war many scientists
had imagined.
“We discovered that two molecular motors – dynein and kinesin
– do not compete for control, even though they want to move the
same cargo in opposite directions,” said Paul Selvin, a professor
of physics at the University
of Illinois at Urbana-Champaign and corresponding author of a paper
to appear in the journal Science, as part of the Science Express Web
site, on April 7. “We also found that multiple motors can work
in concert, producing more than 10 times the speed of individual motors
measured outside the cell.”
Dynein and kinesin are biomolecular motors that haul cargo from one
part of a cell to another. Dynein moves material from the cell membrane
to the nucleus; kinesin moves material from the cell nucleus to the
cell membrane. The little cargo transporters accomplish their task by
stepping along filaments called microtubules.
To measure such minuscule motion, Selvin and colleagues at Illinois
developed a technique called Fluorescence Imaging with One Nanometer
Accuracy. The technique can locate a fluorescent dye to within 1.5 nanometers
(one nanometer is a billionth of a meter, or about 10,000 times smaller
than the width of a human hair). Recent improvements to FIONA now allow
scientists to detect motion with millisecond time resolution.
Selvin’s team used FIONA to track fluorescently labeled peroxisomes
(organelles that break down toxic substances) inside specially cultured
fruit fly cells. This was the first time the imaging technique had been
used inside a living cell.
“Our measurements show that both dynein and kinesin carry the
peroxisomes in a step-by-step fashion, moving about 8 nanometers per
step,” said Selvin, who also is a researcher at the Frederick
Seitz Materials Research Laboratory on the Illinois campus.
“Because we see a fairly constant step size, we don’t believe
a tug of war is occurring,” Selvin said. “If the dynein
was fighting the kinesin, we would expect to see a lot of smaller steps
as well.”
The researchers also noted that faster movements occurred with the same
step size, but with greater rapidity. When measured outside the cell,
kinesin moved about 0.5 microns per second. Inside the cell, the speed
increased to 12 microns per second.
“There must be a mechanism that allows the peroxisomes to move
by multiple motors much faster than independent, uncoupled kinesins
and dyneins,” Selvin said. “It appears that motors are somehow
regulated, being turned on or off in a fashion that prevents them from
simultaneously dragging the peroxisome.”
In the future, Selvin wants to combine FIONA and an optical trap technique
to monitor the speed and direction of a peroxisome, and the force acting
upon it.
“By measuring force we can determine how many molecular motors
are working together,” Selvin said. “This will help us further
understand these marvelous little machines.”
Collaborators on the study included Illinois graduate students Comert
Kural and Hwajin Kim (lead authors), Illinois professor of cell and
structural biology Vladimir Gelfand (now at the Northwestern University
School of Medicine) and postdoctoral research associates Sheyum Syed
at Illinois and Gohta Goshima at the University of California at San
Francisco.
The work was funded by the National Institutes of Health, the National
Science Foundation, and the U.S. Department of Energy.
Editor’s note: To reach Paul Selvin, call 217-417-6101; e-mail: selvin@illinois.edu.