The new age of bioimaging — Page 5 of 7 <
Back Next
>
Entering
the third dimension
In Neil Kumar’s study, cells crawled across the
surface of a matrix, traveling in a single plane. Muhammad
Zaman wondered how they would behave in the middle of
this material. Would they move at the same speed and
in the same direction? Would they stay the same shape?
He developed a model based on a series of calculations
about what the two-dimensional model missed, and designed
an experiment to test it.
 |
Muhammad Zaman |
Like Kumar, he grew two lines of cells—one with
normal levels of a protein associated with metastasis
and one with high levels. The projects then diverged.
Zaman worked with prostate cells rather than breast
cells. He dropped the prostate cells into a thick, soupy
matrix, and placed them under a special confocal microscope,
which divided each specimen into virtual slices. A laser
scanned the slices separately at regular intervals,
generating a new stack of images every 15 minutes.
| “Two-dimensional models ignore the obstacles
that cells face in their natural contexts,”
says University of Texas professor Muhammad Zaman.
“In 3D, cells move through a thick jungle
of fibers or ‘vines’ that hinder forward
progress.” |
Zaman collected these series of 3D images for months.
While the Cellomics KineticScan microscope in Kumar’s
study photographed 96 samples at a time, the confocal
microscope scans just one at a time.
But the hard work paid off. After quantifying the movement
of the cells, Zaman found that they behave completely
differently in 3D, confirming his hypothesis. The online
early edition of Proceedings of the National Academy
of Sciences published the results in July.
“Two-dimensional models ignore the obstacles
that cells face in their natural contexts,” explains
Zaman. “In 3D, cells move through a thick jungle
of fibers or ‘vines’ that hinder forward
progress.”
Cells must either squeeze through or chop up these putative
vines to get anywhere. As a result, they move slower
in 3D.
In an interesting twist, all cells need at least some
vines to move, as they stick onto the “branches”
with adhesive-like proteins called integrins and pull
themselves forward. When
Zaman reduced the adhesiveness, in a manner analogous
to certain anti-cancer drugs, the cells moving across
the top of the forest canopy (in two dimensions) needed
a greater number of vines to keep up their pace, while
cells plowing through the jungle needed vines chopped
to maintain the same speed.
Though he uncovered key differences in the way cells
behave in two and three dimensions, he also discovered
a similarity. In a given setting, prostate cells with
high levels of the receptor associated with metastasis
always moved faster than normal cells. But the physical
and chemical composition of the matrix reduced the persistence
of their movement in 3D.
“If you plunk a car down in Cambridge, step on
the gas and drive around in circles, you’re still
stuck in Cambridge. If a cancer cell does the same thing,
then it can never start a tumor in a new location,”
says Lauffenburger. He believes pharmaceutical companies
will eventually adopt 3D models to study how drugs affect
metastasis.
| Written by Alyssa Kneller |
|
|
