A competition between stickiness and speed

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.