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  5. Focus on new faculty: Michael Murrell, using photographs to understand mechanical forces in cells

Focus on new faculty: Michael Murrell, using photographs to understand mechanical forces in cells

“It all begins with a picture.”

While many may not see beauty in laboratory science, Michael Murrell sees the biological materials he studies as beautiful.

A majority of the work he does involves taking pictures while working under a microscope.

“Everything is in a picture,” says Murrell, who joined the Department of Biomedical Engineering and the Department of Materials Science and Engineering as an assistant professor in fall 2013.“Much of what we learn about the physics of these materials and their interactions can be understood from a picture.”

The materials Murrell is referring to are biomimetic and living cells. Murrell studies how living cells and tissues produce mechanical forces. His research group, the Laboratory of Living Matter, does this in two ways. The first is by creating a biomimetic cell.

A biomimetic cell is an imitation of a cell, created from scratch. Murrell explains that cells have 20,000 genes, which produce proteins, many of which are not directly related to the mechanical aspects of the cell. He and his students isolate the components that are responsible for the mechanical properties of the living cell and then reassemble them to create a simplified, non-living cell.

“So we take those components out, we mix them back together, we add chemical energy to resurrect them together in a biomimetic cell,” Murrell says. “Now we’ve got something that looks like a cell and, hopefully, acts like a cell.”

Next, Murrell makes the biomimetic cell do something that a cell would normally do and then analyzes the mechanics related to why the biomimetic cell acted in a certain way.

“You can more easily modulate a biomimetic cell to understand how physical and chemical variables influence an observed behavior. Because there aren’t upwards of 20,000 components in the biomimetic cell: there are something like five,” Murrell says. “You can reproduce cell-like behavior and then vary the internal composition to see how each of those individual components plays a role in that behavior.”

The second method Murrell and his students use to study mechanical forces in cells is to work with living cells and tissues and influence them to produce forces.

As part of his work Murrell creates images like this one depticing actin, a protein that helps cells maintain their shape.

Murrell, however, says there are some issues with working with living cells.

“If you wanted to mechanically probe a cell, you would poke it. Well, you could do that, and you might be able to measure its mechanical properties, but then when you do that the cell is going to mount a response to that perturbation. It says there’s a problem here, and so it changes the internal, biochemical landscape of the cell, which thereby changes the mechanical properties of the cell the next time around,” Murrell says. “It can interfere with the direct understanding of the mechanical properties of this cell because it’s confounded in there with its stress response, or with its general metabolism.”

This is the main reason Murrell isolates only mechanical parts of the cell to create a biomimetic cell.

According to Murrell, mechanical forces in cells have extremely important implications.

“Everything from the development of embryonic tissues to cancer metastasis involves the generation of mechanical forces, and depends heavily on the mechanical properties of cells,” Murrell says. “If for example, we understand how cells generate forces, we may be able to discover novel regulators of those forces. This would for example, provide new avenues for interrupting cancer metastasis and other pathologies.”

Murrell began by studying physics, and in college he considered what kind of contributions physics, or materials science might be able to make to biology.

“I have tried many different fields of study, and I fell in love with the overall approach and scientific philosophy I was exposed to as a postdoc,” Murrell says.

According to Murrell, who studied at the Institut Curie in Paris, France, this technique for studying a cell’s mechanical properties is more mainstream in Europe. Murrell learned this method while studying in Paris.

“The field is much more developed in France and in Germany for example, than in the United States,” Murrell says. “It’s sort of a different philosophy. It stems from the history of physics and materials science that has developed in Europe.”

However, Murrell chose not to stay in Europe. He came to UW-Madison in Fall 2013 with a hope to work with leading experts in cell biology, who would compliment the techniques he had previously learned.

Although primarily a biomedical engineer, Murrell strives to run a multidisciplinary lab.

“My dream is to have almost equal parts physicists, engineers, biologists and biochemists,” Murrell says.

Jasmine Sola