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:: By Brooke E. O’Neill, AM’04

:: Photo by Lloyd DeGrane

:: Image courtesy Margaret Gardel

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Investigations ::

Intracellular choreography

Biophysicist Margaret Gardel investigates how flexible matter helps cells merge and morph.

In a healthy human body, cells assemble and disassemble, divide and reproduce, through an intricate dance. Pools of gelatinous cytoplasm, the substance that fills most animal cells, provide the stage. Regulatory proteins choreograph each performance, organizing thin microfilaments into a network known as the cytoskeleton. Strong yet malleable, this cellular scaffolding can transmit and withstand the external forces a cell body requires to move and alter its shape. Through this movement, the cell harnesses chemical energy, powering activities such as cell division and migration.


Margaret Gardel studies how cells’ internal scaffolding affects human disease.

Yet a single misstep caused by improper regulation can throw off the entire production. Whether stricken by cancer or cardiac disease, “most everything you can imagine might happen does happen” when it comes to diseased cells, says biophysicist Margaret Gardel, an assistant professor of physics who studies the biological properties of the cytoskeleton. Cancers, for example, may spread because of faulty cytoskeletal control of cells’ migration. A cancer cell may grow protruding structures and migrate when it shouldn’t, traveling out of a tumor mass and into the bloodstream.

For Gardel, understanding how the cytoskeleton functions in both healthy and unhealthy cells means having a clear grasp of its physical nature. Constructed of semiflexible protein filaments, the cytoskeleton, she explains, shares traits with substances like shaving cream and Silly Putty. Unlike hard materials—metal or crystal, for example—these soft substances bend and shift at room temperature. Heat fluctuations that would not affect the integrity of a hard substance can produce large-scale rearrangements in soft matter. Combining cell biology and physics, the study of these materials makes up a growing subfield known as soft condensed-matter physics.

To illuminate how cellular structures function, Gardel, who joined Chicago after receiving a PhD in physics from Harvard University in 2004, uses high-resolution light microscopy to peer inside the cell and examine proteins regulating cytoskeletal movement. Injecting a fluorescent protein into a live cell, she creates “a little lightbulb” to observe internal motion. The process is recorded as time-lapse movies: proteins moving, dividing, and generating force. Inside each cell, different proteins convert chemical energy into shape changes, fueling functions such as DNA replication and chromosome division.

The work is promising. In March Gardel won a $50,000 research fellowship given to young science faculty by the Alfred P. Sloan Foundation. The award supplements a $2.5 million NIH Director’s Pioneer Award she won last September and will fund her cytoskeleton investigation.


Gardel injects cells with fluorescent proteins to light up their internal functions. Seen here in green, actin filaments give the cytoskeleton its flexible structure.

“The cell is the most unusual material that you could find,” Gardel says. Unlike the main elements of an inanimate object, the cell does not remain unchanged from day to day. Think about a car, she says: “The cell basically assembles and disassembles its clutch, its engine, its wheels, its whole structure” on a regular basis. Such movement requires a certain elasticity. “Cells need to move, they need to change shape, they adhere to their extracellular matrix to form tissues.”

In the case of diseased cells—especially cancerous ones—proteins may misdirect these physical behaviors. “It’s hard to generalize” how those behaviors may be faulty, Gardel says. “Every single cancer is different.” Despite such variation, she works to provide biomedical researchers with the means to more effectively treat individual disease. While scientists continue to better understand how cells function on a molecular level, says Gardel, “we really don’t know how to translate that molecular information up to the whole tissue level.” Such understanding, she says, may one day allow researchers to design drugs that directly target the proteins controlling cellular ability to contract and expand—behaviors that can become misguided in unhealthy cells.

For now, Gardel focuses on identifying how the cytoskeleton structure moves during processes like cell division. With three Chicago colleagues, she is part of a team using a $1.8 million W. M. Keck Foundation grant to study “catastrophic deformation,” a phenomenon that describes the rapid and vast effects of small structural changes in a physical system. Catastrophic deformation explains, for instance, collapsing sand castles, mudslides, and avalanches. In Gardel’s case, the large-scale rearrangements of interest are those within the cytoskeleton. Cytokinesis, the process of a cell cleaving to form two daughter cells, is one example. To investigate these shape changes, she will record the transformations on microscopes that capture images at a rate of 30 frames per second.

Gardel not only employs advanced research methods; she also helps improve them. In January she published an article in Biophysical Journal analyzing which microscopy and computational techniques best measure the forces cells exert. Using tools like gels and fluorescent marker beads, researchers can gauge what gets displaced when cells undergo shape changes. Biophysical methods that measure cell force and elasticity have historically been confined to different labs from the work of researchers who study cytoskeletal dynamics using microscopes, says Gardel. “We’re trying to combine those two techniques.”

Asked how she got interested in soft condensed-matter physics, she laughs. “I kept studying physics because it was the hardest subject for me,” she says. As an undergraduate at Brown University, she enrolled in physics classes, worked as a lab assistant, and found her way to soft condensed matter after exploring geophysics. Now focused on understanding the cell’s physical properties—the internal choreography that governs every function—she hopes to help demystify the inner rhythms that fuel all living matter.