Nucleus Is Key to How Cells Sense Personal Space
In a pair of papers published in the same issue of Cell in 2015, two groups showed that putting physical pressure on cells—by confining them, for instance—causes previously stationary cells to start moving quickly. But it wasn’t clear how cells translated being squished into relocating. Many of the same researchers, again working in two independent teams, have now found that the nucleus is responsible for sensing changes in pressure and triggering the signaling cascade that leads cells to get moving. Both studies were published today (October 15) in Science.
“Even five years ago, people would shake their heads that the nucleus is nothing but a bowling ball inside of a snake. It was just this big, dense, unnecessary thing the cell had to drag along out of desperation because it had the DNA inside of it,” says Kris Dahl, a chemical engineer at Carnegie Mellon University who was not involved in either study. While there had been prior evidence indicating that the nucleus can pass mechanical forces from one side of the cell to the other, she adds, “these are the first papers to really show that . . . it’s actively contributing, sending signals to the cell to allow it to do things.”
“Similar to people, cells that make up tissues and organs in the human body are actually able to understand and protect their sort of personal space,” explains Alexis Lomakin, a cell biologist at the St. Anna Children’s Cancer Research Institute in Vienna and a coauthor of one of the new studies.
After the 2015 studies, both research groups wanted to understand what signals cause cells to start to move when they’re confined. They’d shown in the earlier papers that contractility of myosin-II proteins just inside the cell membrane in the area known as the cell cortex triggered the movement, but what was sensing the cellular deformation and then activating myosin II was an open question.
Lomakin became a guest scientist in the lab of Matthieu Piel at Institut Curie in Paris in 2015. He wanted to tackle this question of why cells contracted when confined, so he initiated a collaboration with Cédric Cattin, then a graduate student in the lab of Daniel Müller, a biophysicist at ETH Zürich. Cattin, Müller, and colleagues had described a technique in 2015 in which they used microscopic cantilevers to confine cells. Lomakin and Cattin worked together to apply the technique to precisely quantify cell responses to external pressure.