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Normal epithelial cells primed on a stiff matrix

Normal epithelial cells store a mechanical memory of their past matrix stiffness

These normal epithelial cells primed on a stiff matrix store a mechanical memory of their past matrix stiffness and continue to show high expressions of force-generating proteins even after arriving on a soft matrix (actin in red, myosin in green and cell nuclei in blue).

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In the body, cells move around to form organs during development, to heal wounds, and when they metastasize from cancerous tumors. A mechanical engineer at Washington University in St. Louis found that cells remember the properties they had in their first environment for several days after they move to another in a process called mechanical memory.

Amit Pathak, an assistant professor of mechanical engineering and materials science in the School of Engineering and Applied Science at Washington University in St. Louis, spent three years using mechanobiology and materials science to find answers to these questions: If cells sit in one environment and move to another one, do they remember the first one, and do they inherit any of the properties of the first environment?

To prove his hypothesis, Pathak created a device from which he can measure how long the cells' memory lasts in the new environment. The device, which has a U.S. patent pending, has two sides divided by a barrier. Samila Nasrollahi, a graduate student in Pathak's lab, placed cells in the stiff side of the device -- a similar environment to a malignant tumor. After a few days, she removed the barrier and the cells quickly invaded the other side of the device, which is a soft environment. In addition, they found that the cells maintain the properties they had in the stiff environment for three days in the new environment, due to retaining the YAP gene in the nuclei. The YAP gene is amplified in human cancers.

"Removing the barrier could be similar to the process of cancer cells escaping the primary tumor by breaking through the surrounding tissue, which is the genesis of metastasis," Pathak said.

Pathak says the device mimics a tumor environment in the body. "This answers one of the crucial questions in tumor invasion," Pathak said. "If the tumor cell leaves a very stiff active environment and goes to soft surrounding tissue, why don't they stop there, because a soft microenvironment is known to slow migration?"

This research was supported in part by the National Science Foundation (NSF) (grant CMMI 14-54016).

Read more in the NSF News From the Field story Cells' mechanical memory could hold clues to cancer metastasis. (Date image taken: 2016; date originally posted to NSF Multimedia Gallery: May 29, 2018)

Credit: Samila Nasrollahi and Amit Pathak, Washington University

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