[Editors] MIT device draws cells close--but not too close--together

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT device draws cells close--but not too close--together
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For Immediate Release
THURSDAY, MAR. 29, 2007
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

GRAPHIC, MOVIE AVAILABLE

CAMBRIDGE, Mass.--In a popular children's game participants stand as 
close as possible without touching. But on a microscopic level, 
coaxing cells to be very, very close without actually touching one 
another has been among the most frustrating challenges for cell 
biologists.

Now MIT researchers led by Sangeeta Bhatia, associate professor of 
electrical engineering and computer science at the Harvard-MIT 
Division of Health Sciences and Technology (HST) and Brigham and 
Women's Hospital, have solved the problem with a novel device. The 
work promises to allow researchers to perform cellular experiments 
that were previously impossible.

Bhatia and HST postdoctoral associate Elliot Hui describe the device 
in the March 27 online issue of the Proceedings of the National 
Academy of Science. Hui is first author of the paper.

The new device, a microelectromechanical system (MEMS), allows 
biologists to physically arrange cells to be either touching, close 
but not touching, or completely separated from one another. Further, 
they can change that configuration at will. And the device works 
without the use of tools such as the microscopes or robotic control 
arms typically required by MEMS devices.

Because cells communicate via signals transmitted both through the 
touching of cell membranes and through soluble molecules that flow 
between separated cells, biologists need to vary the spacing of cells 
to study their interactions. Also, since some signals induce a cell 
to change its internal programming, it is important for biologists to 
be able to rearrange cells over time to learn which signals spur 
change and which don't.

In the past, researchers erected chemical "moats" around cells in an 
attempt to keep them close but separate. Over time, however, cells 
invariably breech the divide. "They are very good at crossing the 
moat," said Bhatia, who performed several such experiments in 
graduate school.

Bhatia and Hui's first thoughts about how to solve this cellular 
space and time problem involved another children's game: plastic 
puzzles with squares that slide around on a grid. They wondered if 
they could put different cells on each square and then move them 
around.

This idea quickly evolved into an elegant tool designed expressly for 
biologists.

The device involves two separate comb-shaped pieces coated with 
living cells. These two pieces can click into place at two settings: 
One allows cells on the edges of the combs to touch, the other 
maintains a gap of 80 micrometers, or about four cell widths. The 
assembly is geared so that switching between these two settings 
involves a movement of two millimeters, an amount controllable by the 
human hand. Hui selected 80 micrometers as the gap setting because at 
shorter distances, cells sometimes migrate across the gap and end up 
touching. And at wider distances, some soluble signals drop off.

Bhatia and Hui have used the new device to study liver cells. The two 
found that to get liver cells to express specific liver functions, 
they needed to touch supporting stromal cells for 18 hours. For the 
liver cells to survive and continue to act as liver cells, they don't 
have to keep touching these stromal cells, but they do need to stay 
close.

The finding will allow Bhatia and Hui to examine more deeply which 
surface molecules trigger liver cell differentiation and which 
soluble molecules maintain it.

Such information will help the team devise different approaches to 
engineering liver therapeutics by helping them understand exactly 
which signals are needed to support specific liver cell functions. 
Instead of building an entire liver from scratch, Bhatia wants to 
isolate the key cell type, "the business end of the organ," and get 
it to work without replicating the entire cellular environment that 
supports it. "If you can get away with it, you want to get rid of the 
supporting cells," she says.

This simple device will also be useful for exploring a host of other 
cellular interactions. Most prominently, the device could be very 
useful in exploring embryonic development, during which the local 
cellular environment dictates development of major organs over time, 
and cancer, in which supporting cells are thought to play a role in 
tumor formation.

The research was supported by the National Science Foundation, the 
National Institutes of Health and the David and Lucile Packard 
Foundation. Hui was supported by a Ruth L. Kirschstein National 
Research Service Award.

--END--

Written by Elizabeth Dougherty, Harvard-MIT Division of Health 
Sciences and Technology