Harnessing Wrinkles: Using Stem Cells to Divide in Two

What looks like a straightforward task for a cell – divided into two parts – is actually a complex series of engineering puzzles. A dividing cell needs to be maneuvered from the inside so that the correct components end up in each cell to produce two functioning cells.

Ken Prihoda, a biochemist at the University of Oregon, is trying to solve one of those fundamental mysteries: how a dividing stem cell breaks down parts of its membrane during the process of division.

In a new study, he and postdoctoral researcher Bryce Lavoya show how stem cells that are ready to divide create a reservoir of extra membrane, which accommodates the increased surface area needed for two cells. The pair described their findings in a paper published April 27 developmental cell.

Animal cells are surrounded by a thin membrane that forms a protective barrier around the cell. Just before an animal cell divides, it becomes more round, said Prihoda, who is part of the College of Arts and Sciences.

“Engineeringly, the ball is optimal for minimizing the amount of membrane,” he said. “But to divide the cell in two, it is compressed and the surface area increases sharply.”

In this sense, cell division is like discusing a balloon, except that the balloons can expand as they change shape. The cell membrane is not as stretchy as that of a balloon, but it still needs to be able to stretch in some way to accommodate the pressure together and pressure on a new cell.

Prihoda’s team focused on this challenge in neural stem cells, the cells that give birth to cells in our nervous system. As they continue to make new cells, stem cells divide asymmetrically: the stem cell retains most of the cell material, giving little to its new sister cells.

Prehoda and LaFoya used a rotating disk confocal microscope equipped with advanced super-resolution technology to look inside the brains of developing fruit flies. Lavoya notes that the membranes of neural stem cells are decorated with small folds and bumps, “a kind of extra skin on wrinkly dog ​​breeds like Shar Pei and bulldogs,” he says.

Lavoya realized that the membrane of neural stem cells uses these “wrinkles” to hold the membrane when it is needed during division. As Lavoya watched the cells divide, he was amazed to see wrinkles gathering on one side just before the division. The location of the wrinkle determines where the cell can grow and where the new cell can form.

While asymmetric division allows a neural stem cell to give up only a small portion of its resources, asymmetry makes membrane division a particularly difficult problem. Lavoya points out that Cell has found a great solution to this part of the engineering puzzle.

“Making the extra membrane in advance and positioning it properly before partitioning is an elegant solution that we couldn’t have imagined before starting this project,” he said.

This is just one question among many that Prihoda and his lab are trying to answer using advanced microscopy techniques, which allow them to look at cells at new levels of detail. Thanks to this new technology, Prihoda said, “we have an Embarrassment of Riches, and a lot of new images to explore.”