• Research

Mighty Microscopic Fibers Key to Cell Division and Life Itself

By Levi Gadye

Every second, millions of cells in your body divide in two. In the space of an hour, they duplicate their DNA and grow a web of protein fibers around it called a spindle. The spindle extends its many fibers from the chromosomes in the center to the edges of the cell. Then, with extraordinary force, it pulls the chromosomes apart.

How the spindle accomplishes this without destroying itself has long been a mystery.

Now, scientists at UC San Francisco have discovered that the spindle can repair itself as it’s pulling on the DNA, replacing weak links while it’s working. This constant reinforcement ensures that the DNA is divided exactly in two, avoiding putting even one extra chromosome in a cell that could lead to cancer or birth defects.

“We know that the spindle, which generates a lot of force, must be incredibly strong, but it’s tough to measure that strength directly,” said Sophie Dumont, PhD, a professor of Bioengineering and Therapeutic Sciences and Biochemistry and Biophysics at UCSF and the senior author of the paper. “Our study gives us a glimpse into why this molecular machine is so dependable.”

The paper appears in Current Biology on Jan. 23.

To see how the fibers buckled under pressure, UCSF graduate student and first author Caleb Rux stressed them to their limit with a tool called a microneedle. Made from glass stretched to be finer than a human hair, the microneedle had a smooth end to avoid puncturing the cell, which would have killed it.

Peering through a microscope, Rux would hunt for an elongated cell that was poised to divide — spindle stretching end to end with chromosomes at its center. Using a remote control, like the X-Y dials of an Etch-a-Sketch, he positioned the microneedle above a spindle fiber. He used a third dial to lower the needle and took his hands off the controls.

Then, he switched on a finely calibrated motor that made the needle pull gradually on the fiber until it snapped.

“We expected the spindle fiber to break at its ends, but instead, it snapped where the needle was pulling,” Rux said.

A thin glass needle (red dot in left, blue area in right) stretches a single fiber of the spindle, the molecular machine that separates chromosomes as a cell divides. Using this technique, UCSF researchers discovered that spindle fibers become sturdier after initially buckling under force, a remarkable example of self-repair in a living system. Credit: Caleb Rux, Dumont Lab

What’s more, the broken end kept its shape without retracting or falling apart. This was a big surprise, since in an earlier experiment the team had found that zapping a fiber with a laser would cause it to disintegrate.

Further tests explained why. When the spindle initially stretched against the needle, some of its protein links fell out. But the fiber immediately replaced them with even stronger links that were floating nearby, bracing itself against the physical challenge.

By the time the spindle snapped, it was stronger than before.

“We’re excited about this because it could mean that the spindle stabilizes itself where it’s under most force,” Dumont said. “If you’re a structural engineer, you want buildings to survive earthquakes, roads to survive many winters. Maybe there’s something more we could learn from the self-repairing materials of the living world.”

Authors: Other authors are Megan K. Chong, PhD, Valerie Myers, and Nathan H. Cho.

Funding: This work was supported by the National Institutes of Health (R35GM136420), the National Science Foundation (NSF Graduate Research Fellowship Program, 1548297) the UCSF Discovery Fellowship, the UC Berkeley/UCSF Bioengineering Community Fellowship, H2H8 Research Grant, and the Chan Zuckerberg Biohub.