How single cells work together to create a tissue is major question across biomedical sciences. Engineering professor Eric R. Dufresne applied tools from engineering and physics to address the critical question of how the mechanical properties of cells are altered when multiple cells cooperate in a colony.

 
Dufresne, physics doctoral candidate Aaron F. Mertz, biology professor Valerie Horsley, and colleagues at Yale and Syracuse University studied cellular interactions from a physical point of view – something that’s primarily been done on the single-cell level in the last 15 years, leaving a major area of inquiry unaddressed.
 
“Biophysicists have studied whole tissues and single cells, but what happens in between is not yet well understood,” says Mertz, lead author of the paper appearing in the May 11 edition of Physical Review Letters. “We examined how cells cooperate mechanically on a scale between those two systems.”On the right: Two keratinocytes, cells from the basal layer of the skin, adherent to each other through a strong cell-cell adhesion, shown in red
 
Using a technique called traction force microscopy, the researchers measured the distributions and magnitudes of mechanical force exerted by colonies of skin cells on a squishy surface. Basically, they studied how groups of cells stick to and pull on the surfaces. The researchers found that, from this point of view, a single large cell functions the same way as a colony of many cells that’s the same size: in other words, the force exerted by a group of cells is not sensitive to the number of cells, but to the physical size of the group. The team was surprised to find that these groups of cells behave mechanically much like a droplet of liquid sitting on an elastic surface.
 
“Surface tension is an essential concept for simple liquid droplets,” says Dufresne, “And we’re surprised to find that it can be relevant to complex living groups of cells.”
 
Looking at cells from a mechanical point of view at this size scale could have applications in wound healing and even work as a model for how cancer spreads.
 
“We think that the physical concepts of surface tension might provide a valuable perspective for understanding and preventing metastasis,” says Dufresne.
 
When cancer metastasizes, cells from a tumor break away and migrate to another area of the body. “Surface tension might be a way for us to quantify the metastatic potential of a tumor,” says Mertz. “A droplet of liquid or a colony of cells with a high surface tension is more likely to stick together, whereas a cell from a colony of low surface tension is more likely to break away.”
 
“Being able to quantify particular adhesion forces is a powerful technique to further our understanding of cell cooperation, because many different types of adhesions can affect the overall cohesiveness – or ‘stick together-ness’ of cells,” explains Horsley. The ability to measure specific forces lets researchers study what happens when those forces change – and in fact, that’s just what Mertz wants to do next.
 
“I think our findings in these small colonies of cells are dependent on their having very strong contacts between the cells – that’s what gives rise to the colony’s cohesiveness,” says Mertz. “In my future work, I want to break down that cohesiveness and look at what happens to the physical properties we’ve been measuring and how that picture changes in cell systems that might model cancer metastasis.”
 
Interdisciplinary research such as this is not new to Dufresne; his position at Yale – John J. Lee Associate Professor of Mechanical Engineering & Materials Science, Chemical & Environmental Engineering, Physics & Cell Biology – reflects his wide range of expertise and interests. For his part, he believes that looking at the same problem from the perspective of two different fields is how to truly make advances in both.
 
“It was shocking to us that a collection of cells can behave like a liquid droplet.,” Dufresne says. “Now that this basic physical behavior is established, we need to understand the biology of how and why cells are doing this.”
 
Read the paper at Physical Review Letters: Scaling of Traction Forces with the Size of Cohesive Cell Colonies.
 
Source: Yale News & Events - http://seas.yale.edu