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April 19, 2021

by Allison Gasparini, Stanford University

In your body, cell movement plays a critical role in many important biological processes, including wound healing, immune responses, and the possible spread of cancer.

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“Most people don’t die from a primary tumor,” said Kolade Adebowale, a PhD student in chemical engineering and a graduate student in Chemical Biology Interface (CBI) in chemistry, engineering & Medicine for Human Health (ChEM-H) at Stanford University . “The problem is when cancer cells from the tumor acquire the ability to metastasize or move to different parts of the body.”

To advance cell migration studies, Adebowale and colleagues in the laboratory of Ovijit Chaudhuri, associate professor of mechanical engineering at Stanford, worked to develop and test new types of materials that accurately mimick the real tissue that surrounds the cells. New findings building on this work, published April 19 in Nature Materials, improve the “textbook” view of cell migration and provide better insight into the effects of the elastic and viscous properties of a material on cells.

” We found that it makes a big difference whether the cancer cells are on a very rigid plastic or whether they are on a soft and viscoelastic material like a Jell-O, “said Adebowale, the paper’s lead author. “This contributes to much recent evidence that cancer behavior is not just about the cancer cells, but also the environment with which the cancer cells interact.”

Traditionally, cell migration has been studied on a hard, transparent piece of polymer referred to as “tissue culture plastics” or elastic hydrogels such as soft contact lenses. Based on these studies, it is currently believed that cells cannot migrate on hydrogels that are too soft. However, the researchers want to imitate the real biological tissue on which cells migrate – which are soft and not purely elastic like a rubber band, but rather viscoelastic.

“They are solid materials, but also have viscous and liquid properties that make them allow them to flow for longer periods of time, “said Adebowale.

Examples of viscoelastic materials made for research include bread dough, mozzarella, and silly putty, according to Chaudhuri. These materials initially resist deformation like an elastic material, but viscously relax this resistance over time.

When the researchers examined the movement of cancer cells on their more tissue-like substrate, the results contradicted existing expectations.

“We found that when the substrate is viscoelastic, the cells can migrate fairly robustly despite being soft,” said Chaudhuri, the paper’s lead author.

The study found not only that cells on soft, viscoelastic substrates can migrate, but the researchers also discovered that the migratory movement is unique. On a rigid, 2D surface such as tissue culture plastic, cells adhere to the surface and form a fan-like protrusion. This protrusion, called a lamellipodium, propels forward movement by stretching the leading edge forward and pushing it off the surface. With the viscoelastic materials created by the team, the cells did not spread as much. Instead, they used thin, pointy-like protrusions called filopodia to encourage their movement. Furthermore, their experiments showed that the cells use what is known as “molecular coupling” to migrate on the substrates.

“Imagine moving on ice. If you do not have enough adhesion to the ice and try to run, you will have nowhere to go, “said Chaudhuri. “You really need a strong grip to push off and move forward. That is exactly what the molecular coupling does for cells.”

Robust, migrating cells on rigid tissue culture plastic form strong adhesions to the substrate. The authors observed that cells can also migrate robustly on soft, viscoelastic substrates, but most importantly, these cells can do so with less weak adhesions – just like the cells move on their tiptoes, not their entire foot.

” I think what was most surprising was that the material property – the viscoelasticity – can have such a dramatic impact on the ability of cells to migrate, “said Adebowale.

The fact that the type of cell migration observed by the researchers is not observed on hard or just elastic substrates shows how important viscoelasticity is to the behavior of cells – and therefore important to replicate it in future studies.

“This questions the textbook view as we do Understand cell migration, “said Chaudhuri. “Cells migrate differently on viscoelastic tissue than they do on glass, plastic petri dishes or elastic gels. So if we want to study cell migration, we have to use viscoelastic substrates.”

While the study looked at the migration of individual cells, cancer cells migrate as a group in the body and various stages of development involve the collective movement of cells. Next, the researchers hope to answer the question of how viscoelasticity affects collective cell migration.

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Ref: https://phys.org