It’s crowded inside your body. Many of the trillions of cells in your body are surrounded by neighboring cells and other biological material to form complex and functional tissues.
And when the time comes for a cell to divide and reproduce itself, a process known as mitosis, the mother cell must push against its surroundings to make room to copy itself and produce a daughter.
For Ovijit Chaudhuri, assistant professor of mechanical engineering at Stanford, this well-understood biological process raised an intriguing question. “For many cells in our tissues, there is little to no room to spare, yet somehow cells find a way to divide,” he said. How?
The traditional way of studying mitosis, examining cells in petri dishes, had taught scientists very little about how cells generate space to allow cell division to occur inside the body. So Chaudhuri and colleagues figured out a way to study mitosis in something approximating a more lifelike environment.
Working with Sungmin Nam, a doctoral candidate in his lab, Chaudhuri developed a benchtop experimental environment in which cells divide in a transparent, water-based polymer gel — a hydrogel — that provides tissue-like elasticity. They embedded the gel with fluorescent microbeads that glow red when illuminated with green light, which allowed them to visualize in three dimensions how dividing cells deform, or push against, the hydrogel. By measuring the displacement of the beads, they were able to estimate the amount of force being exerted by the dividing cell.
“We were able to see clearly that dividing cells pushed strongly outward on the surrounding gel along the axis where the chromosomes align and separate as they divided,” Chaudhuri says.
They found that the dividing cells create this protrusive force in two key ways. First, they push outward along the axis where the chromosomes line up using a structure known as the mitotic spindle. The chromosomes carry the DNA for the two daughter cells. The spindle elongates during cell division, pushing outward like a tent pole.
Next, the mother cell forms a contracting ring around its equator like a tightening belt that eventually splits the mother cell into two daughter cells. As the cell does this, the cell’s exterior membrane begins to bulge outward at either end, generating additional outward force.
“This is similar to what happens when you squeeze a water balloon in the middle — the balloon will then extend out at both poles,” Chaudhuri explains.
The forces from elongation and squeezing at the middle are usually enough to push aside neighboring materials and allow the cell to divide. But Chaudhuri and Nam learned another key detail: that cells will not reproduce if the forces pushing back are too strong. “If it’s too crowded and the cell cannot push strongly enough to create space, the cell will not divide. Some of these cells that fail to divide will then go on to die,” Chaudhuri says.
They reported these findings in Nature Physics.
Chaudhuri’s goal, he says, is to advance our basic scientific understanding of mitosis. However, the insights from their work may also lead to new treatments for cancers. Fast-growing tumors not only must create room to expand within the original tissue where they form, but they also grow with deadly consequence in other parts of the body where they do not belong. “We may be able to find drugs or other ways to target these mechanical processes to stop cancer,” says Nam, the first author of the paper. “If cells can’t divide, a tumor can’t grow.”