Northeastern University

A competition between stickiness and speed

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Earlier this year, I wrote a News@Northeastern story about Anand Asthagiri, a chemical engineering professor who is interested in how cells move around the body. The process, he says, is critical to understanding how wounds heals and diseases, such as cancer, reach a lethal metastatic stage. If we know what makes cells moves, we might be able to coax them into doing it–or not doing it–when we want them to, in applications such as tissue engineering.

In an article released in the journal of the Public Library of Science a couple months ago, Asthagiri looked at cellular aggregation, another fundamental element of development and tissue repair.

The standard thought on how cells come together and form groups has been this: if the matrix along which cells are traveling is stickier than the cells are to each other, they will not form aggregates. If the cells are stickier than the matrix, they will. “It’s a competition between their stickiness to each other and to the materials they’re on,” said Asthagiri. This makes a certain amount of sense, but he supsected there was an element of cell motility missing from the story.

The rate of cellular movement should also have an important role, he said. After all, it doesn’t matter how sticky the cells are to each other if they never come into contact in the first place.But the question remained: does adhesion or motility determine the rate of aggregation?

To figure out the answer, Asthagiri and his graduate student, Melissa Pope (now a post doc at University of Colorado Boulder) first needed to figure out the lifetime of cell-cell interactions. They sat themselves down in front of the microscope and got to work measuring that very thing. As expected, they found that when the matrix was stickier, the interactions were shorter.

But that still didn’t complete the story, because different cell types move at different speeds. The cells Asthagiri and Pope were looking at — epithelial cells — crawl along the matrix at a rate slower than that of the typical cell-cell interaction lifetime. So in this case, the rate limiting step is cell motility. If the cells moved faster, the stickiness of the cells to each other would be the limiting factor.

Asthagiri said that this information could be  valuable when researchers are trying to coax cells to join together to form aggregates. They plotted the interaction lifetimes and the speed at which their cells move on different substrates. Researchers can use that chart to locate an ideal adhesivity for your surface depending on what you want to do (promote aggregation or scattering of cells, for example).

Below are two videos in which Asthagiri and Pope used these new findings to do each of those things. In the first, aggregation is promoted and in the second, scattering.

 


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