Collagen is an essential protein for living tissue. It forms the stiff scaffolding that provides structure and stability for tissues and the cells within them.
It is also nature’s packaging material, supporting and cushioning cells by alternating between states of elasticity and quasi-fluidity, depending on the physical forces acting upon it.
These seemingly contradictory characteristics—stiff or semi-fluid as circumstances demand—make collagen viscoelastic, similar to Silly Putty.
Now, researchers have learned how the protein transitions between these properties. They discovered that more deformation on the collagen—technically, more strain-stiffening—results in accelerated viscoelasticity as the collagen reverts to a relaxed state.
Scientists think that by targeting mechanical forces acting upon cells, they might be encouraged to grow in particular ways to, for instance, heal wounds or replace tissues carved away during surgery.
“People tend to think that cells only respond to chemical cues,” says Ovijit Chaudhuri, assistant professor of mechanical engineering at Stanford University. “But they are also exquisitely sensitive to mechanical cues, to the relative stiffness of the collagen networks that surround many cells, for example.”
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Chaudhuri applies this physical-force perspective to investigate how the mechanics of the tissue affect breast cancer progression and how the mechanical properties of biomaterials can be engineered to promote tissue regeneration by cells.
“It has been found that enhanced tissue stiffness promotes breast cancer progression and that altered stiffness can even cue stem cells to differentiate in certain ways,” Chaudhuri says. “We’re learning that the mechanics of the microenvironment, mediated through the physical forces cells exert on the microenvironment, play major roles in cell function.”
‘Fishing net’ strands
For the new study, published in the Proceedings of the National Academy of Sciences, researchers investigated the mechanics of collagen networks through traditional mechanical testing, computational modeling, and using atomic force microscopy to apply force at the molecular scale.
Collagen biopolymers are “cross-linked,” meaning they are connected like the strands of a fishing net, says coauthor Sungmin Nam, a mechanical engineering graduate student.
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“These cross-links, however, are not always particularly strong, and can be quite weak. Our work suggests that these weak cross-links exhibit force-dependent unbinding. In other words, the greater the force on the cross-links, the quicker they unbind. So the more force on the collagen in general, the quicker you’ll see a subsequent relaxation.”
Cell behaviors are deeply influenced by mechanical properties, so the research suggests the mechanics of collagen could play a big role in regulating cell behaviors.
“We know that cells interact strongly with their microenvironments, and that (collagen) polymers affect these microenvironments through strain-stiffening and viscoelasticity,” Nam says. “As we gain insights into cell-collagen interactions, it could help us develop new techniques for 3D cell culture and tissue regeneration.”
The National Institutes of Health, the Stanford Child Health Research Institute, and DARPA supported the work.
Source: Glen Martin for Stanford University
