NOT A HARD CELL: Dan Fletcher with a custom Atomic Force Microscope designed and built by his research group to analyze the mechanisms of cell motility.

BioE professor speaks on cell research at Berkeley in Silicon Valley event

A cell is an engineering tour de force, perfected through four billion years of research and development. That’s why many diseases are so tough to beat. Fortunately, researchers like Berkeley bioengineering professor Daniel Fletcher are developing new techniques to deepen our understanding of a cell’s mechanical properties. Teasing out those underlying engineering principles could pay off with new drugs that throw a wrench into the works of diseased cells.

“Much of my research is aimed at developing techniques that help us understand the mechanics of cells and proteins and their role in diseases,” says Fletcher, who will present his research at the Berkeley in Silicon Valley symposium on April 24.

Currently, Fletcher is studying the cellular mechanisms underlying giardiasis, a severe diarrheal illness prevalent in many developing countries, and leukemia, a cancer originating in bone marrow that results in the uncontrolled accumulation of immature and malfunctioning white blood cells. Some types of leukemic cells have been found to clog small blood vessels, resulting in strokes and respiratory failure.

“A white blood cell that’s ten microns in size needs to deform to fit through a blood vessel that’s several microns smaller in diameter,” says Fletcher. “But if leukemic cells aren’t flexible enough, they won’t make it through and can aggregate in the vessel.”

Fletcher employs the tools of nanoscience and biology to probe the abnormal cells much as an auto mechanic examines a car’s engine.

For example, a fluorescence microscope hits a sample with a special high-intensity light that causes it to glow, resulting in a vivid image of structural proteins in a cell that’s then magnified by the instrument. Meanwhile, an atomic force microscope physically scans a sample much like a needle travels across a record. As the probe moves over the surface of a cell, a cantilever at the end of the tip bends in response to the sample’s topography and mechanical properties. That deflection is captured by a laser and translated into a measurement with nanometer (one-billionth of a meter) resolution.

In the case of leukemia, Fletcher and graduate students Mike Rosenbluth and Wilbur Lam are using the instruments to measure the flexibility of various types of diseased cells. Comparing those measurements with clinical data will reveal whether the clogs are in fact related to stiffness, stickiness, or some other mechanical property of certain leukemic cells.

Eventually, Fletcher says, a leukemia patient’s blood sample could be analyzed to determine if the cells are in a category of stiffness that’s likely to cause aggregation in the blood vessels.

“If a patient is known to be at risk, steps can be taken to treat the patient before vessels become clogged,” he says.

Written by David Pescovitz

It’s free for students to hear Fletcher speak at the all-day Berkeley in Silicon Valley event on April 24 in Santa Clara. RSVP at eas@coe.berkeley.edu with your name, year and e-mail address to get more info.

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