Researchers identify how cells move faster in mucus than in blood

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Some cells move faster in thicker liquid — think honey versus water, or mucus versus blood — because their ruffled edges sense the viscosity of their surroundings and adapt to increase their speed.

This is one of the surprising findings of a new study published in Natural Physics by researchers from the University of Toronto, Johns Hopkins University and Vanderbilt University.

The researchers’ combined findings on cancer and fibroblast cells – the type that often scar tissue – suggest that the viscosity of a cell’s surrounding environment is an important contributor to disease and may help explain progression. tumor, scarring in mucus-filled lungs affected by cystic fibrosis, and the healing process.

3D rendering of breast cancer cell increasing area of ​​spread when adding viscous fluid. Color code for height, where cooler colors are higher. The rendering was created from a confocal z-stack timelapse of a breast cancer cell transfected with eGFP-F-tractin. A viscous fluid was added at 3.22 s. Video displayed at 25 fps

“This link between cell viscosity and attachment has never been demonstrated before,” says Sergei Plotnikov, an assistant professor in the Department of Cellular and Systems Biology in the Faculty of Arts and Sciences at the University of Toronto and co-corresponding author of the study. “We found that the thicker the surrounding environment, the more strongly the cells adhered to the substrate and the faster they moved – much like walking on an icy surface with spiked shoes, compared to shoes with no adhesion at all. .”

Understanding why cells behave in this unexpected way is important because cancerous tumors create a slimy environment, which means spreading cells can move faster through tumors than non-cancerous tissue.

Since the researchers observed that cancer cells accelerate in a thickened environment, they concluded that the development of ruffled edges in cancer cells may contribute to the spread of cancer to other parts of the body.

Targeting the spreading response in fibroblasts, on the other hand, may reduce tissue damage in mucus-filled lungs affected by cystic fibrosis. Because ruffled fibroblasts move quickly, they are the first cell type to move through mucus to the wound, contributing to scarring rather than healing. These findings may also imply that by altering the viscosity of lung mucus, one can control cell movement.

“By showing how cells react to their surroundings and describing the physical properties of that area, we can learn what affects their behavior and possibly how to influence it,” explains Ernest IuPhD student in the Department of Cellular and Systems Biology and co-author of the study.

Plotnikov adds: “For example, maybe if you put a liquid as thick as honey in a wound, the cells will move deeper and faster there, thus healing it more effectively.”

Sergei Plotnikov (photo by Diana Tyszko)

Plotnikov and Iu used advanced microscopy techniques to measure the traction that cells exert to move and changes in structural molecules inside cells. They compared cancer cells and fibroblasts, which have wrinkled edges, to cells with smooth edges. They determined that the ruffled edges of the cell sense the thickened environment, triggering a response that allows the cell to break through the resistance – the ruffles flatten, spread out, and cling to the surrounding surface.

The experiment originated at Johns Hopkins, where researchers Yun Chen and Matthew Pittman were examining the movement of cancer cells. Chen is assistant professor of mechanical engineering and senior author of the study, while Pittman is a doctoral student and first author.

Pittman created a viscous, mucus-like polymer solution, dropped it onto different cell types, and found that cancer cells moved faster than non-cancerous cells as they migrated through the thick liquid. To further probe this behavior, Chen collaborated with Plotnikov at the University of Toronto, who specializes in pushing and pulling cell movement.

Plotnikov was amazed at the shift in thick mucus-like liquid. “Normally we see slow, subtle changes under the microscope, but we can see cells moving twice as fast in real time and expanding to double their original size,” he says.

Ernest Iu

Typically, cell movement depends on myosin proteins, which help muscles contract. Plotnikov and Iu reasoned that stopping myosin would stop the cells from spreading. However, they were surprised when evidence showed that the cells still accelerated despite this action. Instead, they found that the columns of the protein actin inside the cell, which helps muscle contraction, became more stable in response to the thick liquid, pushing the edge of the cell further.

Teams are now studying how to slow the movement of ruffled cells through thickened environments, which could open the door to new treatments for people affected by cancer and cystic fibrosis.

Funding for the research was provided by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Canadian Network for Research and Innovation in Machining Technology, the Ontario Graduate Studies, the US Department of Health and Human Services and the US Department of Defense. .

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