[Editors] MIT reveals inner lives of red blood cells

[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 reveals inner lives of red blood cells

--Work could aid research on sickle cell anemia and malaria
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For Immediate Release
MONDAY, OCT. 23, 2006
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

IMAGES AVAILABLE

CAMBRIDGE, Mass.--For the first time, researchers at MIT can see 
every vibration of a cell membrane, using a technique that could one 
day allow scientists to create three-dimensional images of the inner 
workings of living cells.

Studying cell membrane dynamics can help scientists gain insight into 
diseases such as sickle cell anemia, malaria and cancer. Using a 
technique known as quantitative phase imaging, researchers at MIT's 
George R. Harrison Spectroscopy Laboratory can see cell membrane 
vibrations as tiny as a few tens of nanometers (billionths of a 
meter).

But cell membrane dynamics are just the beginning.

Soon, the researchers hope to extend their view beyond the cell 
membrane into the cell, to create images of what is happening inside 
living cells -- including how cells communicate with each other and 
what causes them to become cancerous.

"One of our goals is create 3D tomographic images of the internal 
structure of a cell," said Michael Feld, MIT professor of physics and 
director of the Spectroscopy Lab. "The beauty is that with this 
technique, you can study dynamical processes in living cells in real 
time."

Scientists have long been able to peer into cells using electron 
microscopy, which offers a much higher magnification than a 
traditional light microscope. However, electron microscopy can only 
be used on cells that are dehydrated, frozen or treated in other 
ways. Thus it cannot be used to view living cells.

Quantitative phase imaging, on the other hand, allows researchers to 
observe living cells for as long a time period as they want. After 
years of fine tuning, the MIT researchers can now create images with 
a resolution of 0.2 nanometers. (A red blood cell has a diameter of 
about 8 microns, or 8,000 nanometers.)

So far, the team has focused its attention primarily on red blood 
cells and neurons. Red blood cells are an especially good model to 
study cell membrane dynamics because they are relatively simple 
cells, with no nuclei or internal cell structures, says Gabriel 
Popescu, a postdoctoral associate in the Spectroscopy Lab.

In work that is soon to be published in Physical Review Letters, the 
MIT researchers show that the frequency of cell membrane vibration is 
related to the elasticity of the cell membrane. Elasticity is 
important for red blood cells because they have to be able to squeeze 
through tiny capillaries in the brain and elsewhere, as they deliver 
oxygen.
"The elasticity of these cells is crucial for their function," said Popescu.

It has been known for more than a century that red blood cell 
membranes are continuously undulating, or as Popescu puts it, a red 
blood cell is "effectively a drum in perpetual vibration." This 
undulation offers a chance to study the mechanical properties of the 
membrane, including how the membrane provides the cell with both the 
softness and the elasticity needed to squeeze through narrow 
capillaries.

Red blood cell abnormalities, such as the twisting deformation seen 
in sickle cell anemia, also influence membrane dynamics. The 
researchers are now studying how sickle cell anemia and malaria 
infection affect the mechanical properties of red blood cell 
membranes.

Popescu gave a talk on the blood cell work earlier this month at a 
meeting of the Optical Society of America.

Another group in the Spectroscopy Lab is studying signal propagation 
in neurons. This project, a collaboration with Sebastian Seung, a 
professor of brain and cognitive sciences, and led by Chris Fang-Yen, 
a postdoctoral associate in the Spectroscopy Laboratory, is based on 
the fact that membranes undergo tiny mechanical deformations when an 
action potential (electrical current) travels along the neuron's axon.

The correlation between membrane vibration and electrical activity 
could "give us insight on how networks are organized on a neuron 
level," said Fang-Yen. They are especially interested in studying 
neural networks in the hippocampus, a brain area associated with 
memory.

Quantitative phase imaging builds on an optical phenomenon known as 
interferometry. With this method, a light wave passing through the 
cell is compared with a reference wave that doesn't pass through the 
sample. Combining those two waves creates an interference pattern 
that offers nanometer-scale images of individual cells.

The major problem with interferometry is that the apparatus is highly 
sensitive. Even breathing near the interferometer can disrupt the 
system, leading Popescu to observe that in a typical laboratory 
environment, trying to measure such tiny optical signals is "like 
trying to sense the waves of a jellyfish in a stormy ocean."

One way to overcome that is to mount the system in an isolated 
environment. Another technique, known as the "common path" approach, 
places both arms of the interferometer (through which the light waves 
are traveling) in close proximity so the noise in the signals cancel 
each other out.

Quantitative phase imaging has not yet reached the level of 
resolution that electron microscopy offers, but Feld said he believes 
it will someday.

Other Spectroscopy Laboratory researchers involved in the work are 
Wonshik Choi, a postdoctoral associate; Ramachandra Dasari, principal 
research scientist; Kamran Badizadegan, a faculty member in the 
MIT-Harvard Division of Health Sciences and Technology; Shahrooz 
Amin, a graduate student in electrical engineering and computer 
science; Seungeun Oh, a graduate student in physics; YongKeun Park, a 
graduate student in mechanical engineering; and Niyom Lue, a graduate 
student at the University of Massachusetts College of Engineering.

Michael Laposata and Catherine Best Popescu from Massachusetts 
General Hospital are also collaborating on the red blood cell studies.

This work was funded by the National Institutes of Health and 
Hamamatsu Photonics.

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