Engineering Technique Provides Insight into Cellular Forces

Kris Dahl, a chemical engineering and biomedical engineering professor at Carnegie Mellon University, is using a new method to understand how cells are structured. Her method uses densely packed regions of condensed DNA, known as chromatin, to be used a sensors for cellular force generation. The technique, known as SINK, which stands for sensors from intranuclear kinetics, allowed Dahl and her team to provide physical and biological insights into cells.

Dahl got the idea for the technique from a conversation with Provost James Garrett, a civil and environmental engineer whose research has focused on applying sensors to civil infrastructure. The theory is that, by placing sensors in certain positions, researchers can use resources more efficiently than by placing sensors everywhere. SINK is Dahl’s way of applying that theory to monolayers, or sheets, of cells. By placing a few sensors across a monolayer within different cells’ nuclei, Dahl and her team can observe the properties of DNA across an entire monolayer.

Through looking at how the sensors bound in condensed DNA "jiggle," as Dahl said, she and her team discovered that a change in one cell can impact a larger range of cells around it than was previously thought.

"We thought it would change the cells right next to it, but it turns out it changes at least five cells, maybe up to 10 cells, in every direction," said Dahl, who also is a CMU alumna.

Travis Armiger, who worked with Dahl on the project while he was a doctoral student in chemical engineering, is now a senior scientist at Merck. He said the discovery could be particularly important for diseases such as cancer.

"Understanding how these monolayers of cells behave in response to physical forces, in addition to their response to chemical signals, is critical to understanding disease progression and embryonic development," Armiger said.

Dahl and Armiger published their work in the Journal of Cell Science. Dahl presented that and the work of another paper about DNA damage and repair at the American Physical Society’s (APS) annual conference earlier this month.

Another part of Dahl’s research is how cells interact with one another within a monolayer. Instead of modeling a monolayer as a simple sheet of material, monolayers of cells can be modeled as colloidal crystals, which are self-assembled structures of spheres that assemble with lose interactions rather than tight bonds. Modeling monolayers as colloidal crystals means that the thermodynamics of their assembly are different and that they deform differently from how researchers expected. Instead of stretching like a rubber glove, cell monolayers will form propagating defects because of their loose associations, and the cells’ unique interactions become important in areas such as tissue engineering.

While Dahl and her team have figured out that cells within a monolayer are communicating more broadly than previously thought, they have yet to determine how exactly the cells mechanically communicate with each other. But, more researchers are using her SINK technique to continue to learn about cells and their interactions.

"That’s an exciting area of future research," Dahl said.