Researchers identify how cells move faster through mucus than blood

The University of Toronto, Johns Hopkins University, and Vanderbilt University researchers found that some cells move surprisingly faster in thicker fluid than in thinner fluid, such as honey or mucus instead of blood. This is because the ruffled edges of these cells can sense the viscosity of their environment and change to move more quickly.

Their combined findings in cancer and fibroblast cells—the type that frequently leaves tissue scars—indicate that the viscosity of a cell's environment plays a significant role in disease. This finding may explain the development of tumors, the formation of scars in cystic fibrosis-affected lungs that are mucus-filled, and the healing of wounds.

Membrane ruffling is a mechanosensor of extracellular fluid viscosity, a study that was just published in Nature Physics, provides fresh insight into the little-studied topic of cell environments.

According to Sergey Plotnikov, assistant professor in the Department of Cell and Systems Biology in the Faculty of Arts & Science at the University of Toronto and a co-corresponding author of the work, "This relationship between cell viscosity and attachment has never been established previously." "We discovered that, similar to walking on an ice surface with spiked shoes as opposed to shoes with little grip at all, the firmer the cells attach to the substrate and the faster they travel, the thicker the surrounding environment."

Because cancer tumors provide a viscous environment that allows spreading cells to enter tumours quicker than non-cancerous tissues, it is crucial to understand why cells act in this unexpected manner. The researchers came to the conclusion that the formation of ruffled edges in cancer cells may aid in the spread of cancer to other parts of the body since they saw that cancer cells accelerated in a thicker environment.

On the other hand, focusing on the fibroblast spreading response may lessen tissue damage in the mucus-filled lungs afflicted by cystic fibrosis. Ruffled fibroblasts are the first type of cells to get through the mucus to the wound because of their fast movement, which contributes to scarring rather than healing. These findings may also suggest that one may regulate cell migration by altering the mucus' viscosity in the lung.

According to Ernest Iu, a PhD candidate in the Department of Cell and Systems Biology in the Faculty of Arts & Science at the University of Toronto and a co-author of the study, "by showing how cells respond to what's around them and by describing the physical properties of this area, we can learn what affects their behavior and eventually how to influence it."

"Perhaps if you inject a liquid as thick as honey into a wound, the cells will migrate deeper and quicker into it, so repairing it more efficiently," continues Plotnikov.

Plotnikov and Iu measured changes in structural molecules inside the cells as well as the traction the cells exert to move using cutting-edge microscopy methods. They contrasted cells with smooth edges to cells with ruffled edges, such as cancer and fibroblast cells. They came to the conclusion that ruffled cell edges perceive the thicker surroundings and react by flattening out, spreading out, and latching on to the surface in order to help the cell break through the barrier.

The study's lead author, associate professor of mechanical engineering Yun Chen, and its first author, PhD candidate Matthew Pittman, started the experiment at Johns Hopkins by first analyzing the motion of cancer cells. Pittman produced a viscous, mucus-like polymer solution, applied it to several cell types, and observed that cancer cells traveled through the dense liquid more quickly than non-cancerous cells. Chen worked with U of T's Plotnikov, an expert in the push and pull of cell movement, to further investigate this behavior.

Plotnikov was astounded by the abrupt shift in pace as he entered the murky liquid. Under the microscope, we often observe sluggish, subtle changes, but in this instance, we were able to observe the cells expanding to double their initial size and moving twice as quickly.

Normally, myosin proteins, which assist in muscle contraction, are required for cell movement. Plotnikov and Iu believed that inhibiting myosin would stop cells from spreading, but they were dismayed to see that the cells continued to expand. Instead, they discovered that the thick liquid caused the actin protein columns inside the cell, which are involved in muscular contraction, to become more stable, further pushing the cell's edge out.

The researchers are currently looking at ways to restrict the spread of ruffled cells in dense environments, which may pave the way for brand-new cancer and cystic fibrosis therapies.

The Canadian Institutes of Health Research, the Canadian Network for Research and Innovation in Machining Technology, the Ontario Graduate Scholarship, the U.S. Department of Health & Human Services, and the United States Department of Defense all contributed funding to the study.

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Materials provided by University of Toronto. Original written by Josslyn Johnstone. Note: Content may be edited for style and length.