Certain human cells move more slowly through thin fluids, like blood, than through thicker fluids, like mucus, according to a new study. The researchers who carried out the study found that these cells use membrane ruffles—protrusions on the surface of the cell—to sense and adapt to their environment. Their findings may help explain phenomena such as tumor progression and wound healing.
Researchers from Johns Hopkins University, the University of Toronto, and Vanderbilt University collaborated on the study, which was published in Nature Physics (“Membrane Ruffling is a Mechanosensor of Extracellular Fluid Viscosity”).
To date, there has been little research on fluid viscosity and cell behavior. Previous studies have shown links between cancer and other diseases with abnormalities in the viscosities of the surrounding microenvironments, suggesting a physiological role for viscosity.
Furthermore, the culture media commonly used to study cells in a laboratory setting are usually much less viscous than the fluids that the cells are immersed in vivo.
With these observations in mind, the research team used bio-compatible polymers to increase the viscosity of culture medium. They then examined the effects of the increased viscosity on different types of adherent cells. The cells responded in a similar—but unexpected—way.
“We found that the thicker the surrounding environment, the stronger the cells adhere to the substrate and the faster they move,” explained Sergey Plotnikov, PhD, an assistant professor at the University of Toronto, and one of the lead investigators on the study. “[This is] much like walking on an icy surface with shoes that have spikes, versus shoes with no grip at all.”
Specifically, the cells in highly viscous environments migrated nearly twice as fast, doubled in spread area, generated greater traction, and increased focal adhesion formation and turnover. They attributed these changes to structures called membrane ruffles, fin-like protrusions that are characteristic of motile cells.
The researchers determined that the ruffles sense the thickened environment, triggering a response that allows the cells to pull through the resistance. The ruffles flatten down, spread out, and latch onto the surrounding surface.
“Our hypothesis is supported by the observation that cells with negligible or inhibited ruffling did not respond to viscosity,” the researchers noted in their article.
More generally, their work also illustrates that the behavior of cells is influenced by biophysical cues, not just biochemical signals. “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,” said Ernest Iu, a doctoral student at the University of Toronto and one of the study’s co-authors.
“For example,” added Plotnikov, “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.”
The team is also investigating how to slow the movement of ruffled cells through thickened environments, which may open the door to new treatments for people affected by certain types of cancer and mucus-related diseases such as cystic fibrosis.