Imagine that your body is being punched by tiny fists.
This may actually be the case for certain cancer patients. Researchers report in Developmental Cell on June 12 that melanoma cells can mechanically tunnel through tissue utilizing fleshy membrane protrusions without the requirement for toxins that eat up the environment.
Different ways exist for cells to travel (SN: 9/26/18). Some morph their bodies to fit through narrow openings, while others create anchors to pull themselves forward and use proteins to chemically eat away at the surrounding tissue. While it was previously known that melanoma cells might develop protrusions to aid in their movement, computational cell biologist Gaudenz Danuser and associates set out to elucidate the function of these growths.
The cytoskeleton and membrane of cells divide the high-pressure inside from the lower-pressure exterior. There are instances where the cytoskeleton fractures. A bleb is created when the cell membrane is forced outward by the internal pressure.
According to Danuser of the University of Texas Southwestern Medical Center in Dallas, the team was able to record this blebby sort of cell movement by creating a new kind of microscope. The majority of microscopes use hard surfaces to hold samples in place, and this extra pressure might change how cells behave. Instead, a soft gel can be used to encase the cells thanks to the team’s novel microscope.
Pharmacologist Meghan Driscoll of the University of Minnesota Twin Cities in Minneapolis, a coauthor of the study, notes that the researchers observed that the blebs “extend and retract about every 20 seconds.” “The balloons are mechanically destroying enough material over hours to create a tunnel through which the cell can travel.”
The team at Driscoll and colleagues hypothesized that cells are continuously driven forward by a continuous cycle of bleb formation and sensing resistance from the tissue ahead. They observed increased levels of phosphoinositide 3-kinase, an enzyme involved in cell signaling, near the front of the cells.
Anywhere on the cell can generate blebs, but only those that face forward will come into contact with a surface; those that face backward extend into an empty tunnel. The cell can then sense the tunnel surface and indicate where the front is thanks to molecular adhesions that function like tiny feet, according to Danuser. Next, with larger blebs concentrated in the direction of motion, the cell will “amplify the formation of the balloons only where you really need the balloon.”
According to Jeremy Logue, a cancer biologist at Albany Medical College in New York who was not involved in the research, a “pretty novel aspect of this work” is the “mechanically driven type of reinforcement” that prevents the blebs from growing at the front of the cell. “It hasn’t really been appreciated to this level, I think.”
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