Researchers Make Key Finding about Cells

7/3/2012 Kathryn L. Heine

Researchers at MechSE and the Department of Cell and Developmental Biology have discovered the first evidence that mechanical forces play an important role in the invasion of living cells. A paper describing their finding appeared in the online ahead-of-print version of Current Biologyon August 28, and will appear in the journal's September 9, 2008 print issue.

Written by Kathryn L. Heine

Researchers at MechSE and the Department of Cell and Developmental Biology have discovered the first evidence that mechanical forces play an important role in the invasion of living cells. A paper describing their finding appeared in the online ahead-of-print version of Current Biologyon August 28, and will appear in the journal's September 9, 2008 print issue.

Normal cells invade tissues during many normal physiological processes, including organ development, immune and inflammatory response, wound healing and bone remodeling. Similarly, abnormal cells in one tissue invade other tissues during pathological processes such as cancer metastasis and tumor invasion. Recent evidence suggests that the mechanism by which cells invade is regulated by integrin and actin-based structures in the cell membrane known as podosomes (invadopodia in the case of cancer). These structures form close contacts with their surrounding substrates and are believed to be important self-organizing structures for the cell. When a cell invades, it uses these actin-based structures to attach to the scaffolding of the extracellular matrix, dig a hole there, and then squeeze through the resulting hole. How that happens is not entirely understood, yet scientists have speculated that these structures help release enzymes that digest proteins in the extracellular matrix of the cells that are being invaded.

Now, researchers in the Department of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign have discovered the first evidence that mechanical forces play an important role. They described the finding in their paper, "Self-organized Podosomes are Dynamic Mechanosensors," which appeared in the online ahead-of-print version of Current Biology on August 28, and will appear in the journal's September 9, 2008 print issue.The researchers made the discovery by placing yellow-green fluorescent particles in the gel substrate onto which the invaded cells were placed. As an invading cell's podosomes exerted force on a cell, the substrate beneath that cell deformed in much the way a person who lies down on a mattress causes a depression. The fluorescent particles implanted in the substrate moved with the deformation, which allowed the researchers to see the mechanical forces in action. By tracking the movement of these particles, they could watch as the podosomes of one cell moved rapidly inside the cell and then actually poked and prodded its microenvironment. "The cells exerted a force that went all of the way into the scaffolding of the extracellular matrix, and we even detected torsional forces-all in the absence of the whole cell migration," says MechSE Professor Ning Wang. What's more, Wang and his colleagues observed that the stiffer the gel substrate was, the more force the podosomes seemed to exert.

Wang speculates that the cells were using mechanical force to help them sense where they should attach and drill. "They were using mechanical force to tell them where, spatially, they should invade," he says. If so, his group's finding could eventually lead to a better understanding of the way cancer spreads and perhaps even shed light on fundamental questions about how cells organize themselves into the basic units of life itself.


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This story was published July 3, 2012.