The new age of bioimaging — Page 4 of 7 <
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Tracking
cells on the move
A cancer cell breaks away from a tumor and moves to
a new location, where it divides. Mystery shrouds the
mechanics of this process, which is known as metastasis.
But researchers at Whitehead and MIT pieced together
part of the puzzle last spring by making movies and
modeling the movement of the “actors.”
 |
| Neil Kumar |
“We wanted to understand breast cancer better,
so we decided to study a protein called human epidermal
(HER2) because it’s overexpressed in 20 to 30
percent of breast cancers, and it’s correlated
with poor prognosis and increased metastasis,”
explains MIT graduate student Neil Kumar of Douglas
Lauffenburger’s lab.
| “We’re engineers, so it is a natural
goal to characterize the behavior of this system
quantitatively and mathematically,” says MIT
graduate student Hyung-Do Kim. |
Kumar grew two lines of human breast cells—one
with normal levels of HER2 and one with high levels—on
the surface of a gooey matrix in 96-well plates. He
scraped the colonies of cells to create “wounds”
and then loaded the plates into a Cellomics Kinetic-Scan
automated imaging system designed for high-content screening
of cells in motion. This microscope took pictures every
15 minutes for approximately 15 hours.
 |
| Hyung-Do Kim |
Kumar worked with MIT graduate student Hyung-Do Kim
and Whitehead postdoctoral fellow Muhammad Zaman (formerly
a researcher in Paul Matsudaira’s lab and now
an assistant professor at the University of Texas at
Austin) to quantify wound closure in the resulting time-lapse
movies.
“We’re engineers, so it is a natural goal
to characterize the behavior of this system quantitatively
and mathematically,” says Kim.
A quick review of the movies revealed that wounds closed
faster in cells containing more HER2. But the team moved
beyond this crude observation by writing computer programs
that tracked the speed and direction of individual cells.
“Think of a cell as a car moving from point A
to point B,” suggests an animated Kumar. “If
the driver steps on the gas, the car will get to point
B faster. If the driver straightens the steering wheel
and takes a direct path, the car will also get to point
B faster.”
The cells with high levels of HER2 stepped on the gas
mildly, but more importantly dramatically straightened
their steering wheels. Some of the matrixes contained
materials that enhanced this effect, as HER2 is a surface
receptor that responds to environmental cues. Biophysical
Journal published these results in August.
“These findings could have significant implications
for development of anti-cancer therapeutics,”
says Lauffenburger. “We’ve uncovered a level
of cell motility regulation that wasn’t fully
appreciated in the past.”
Lauffenburger likens the discovery to one that scientists
made while modeling cell growth. They began by measuring
changes in the net number of cells. Subsequent work
showed they were glazing over two distinct processes—cell
division and cell death—regulated by a variety
of proteins. Pharmaceutical companies now use some of
the revised models to more accurately predict the effects
of potential cancer treatments.
| Written by Alyssa Kneller |
|
