Why Cells Move Faster Through Mucus Than Blood

At John Hopkins University, two researchers, Matthew Pittman and Yun Chen, discovered something curious about the movement of cancer cells. 

Pittman, a PhD student, had made a mucus-like polymer solution to see how different cell types move through them, and saw that cancer cells migrated faster than non-cancerous cells through the viscous fluid. This prompted Chen, an assistant professor in the Department of Mechanical Engineering, to reach out to Sergey Plotnikov, an assistant professor in the Department of Cells and Systems Biology at the University of Toronto who studied the push and pull of cell movement. 

Shifting Gears in Different Environments

Plotnikov was amazed at the change of speed cancer cells displayed in the thick fluid. Normally, researchers look for slow, subtle changes under the microscope, he reasoned, but what they saw were cells moving twice as fast in real time, and spreading to double their original size. 

Together with Earnest Iu, a PhD student in the same department, Plotnikov used advanced microscopy techniques to measure the traction cells exert to move, as well as changes in their structural molecules. Besides cancer cells, they also looked at fibroblasts, both of which have ruffled edges as opposed to cells with smooth edges. Through experiment, they determined that ruffled cell edges sense viscosity in the environment to trigger a response that allows the cell to pull through the resistance — by flattening ruffles, spreading out and latching onto the surrounding surfaces.

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Stabilizing Actin and Spreading Across Thickened Environments

At first, Plotnikov and Iu thought stopping myosin proteins, which help muscles contract, would slow cell spreading. However, this did not prove to be the case as the cells still sped up. They instead found that columns of actin protein inside the cell, which also help muscles contract, respond to the thickened fluid to become more stable to push out the edge of the cell. 

The researchers’ combined results suggest that viscosity in the extracellular environment plays an important role in disease, and may help explain tumor progression, scarring in mucus-filled lungs affected by cystic fibrosis, and the wound healing process.

Tumors create a viscous environment, helping spreading cells move into the tumor more quickly. The development of ruffled edges in cancer cells may contribute to metastasis, the researchers surmised. 

On the other hand, targeting the spreading response in fibroblasts may reduce tissue damage in the mucus-filled lungs affected by cystic fibrosis. As ruffled fibroblasts move more quickly than other cells through the mucus, they may initiate scarring at the site of the wound instead of healing.  By changing the viscosity of the lung’s mucus, one may be able to control cell movement.

“For example, perhaps if you put a liquid as thick as honey into a wound, the cells will move deeper and faster into it, thereby healing it more effectively,” inserted Plotnikov.

The findings cumulated in a paper titled “Membrane ruffling is a mechanosensor of extracellular fluid viscosity”, which was published in Nature Physics. 

Next, the scientists will investigate how to slow the movement of ruffled cells through thickened environments, which may pave the way for new treatments that target cancer and cystic fibrosis.

Author

Joy Lin

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