A new study from Stanford University shows how collagen, an essential protein for living tissue, transitions between properties--providing insights on how the protein could be used in regenerative medicine.

Kristopher Sturgis

It's no secret that collagen plays a vital role in the structure and stability of tissue and cells in the human body. The protein is packed with unique properties that enabled it to cushion and support tissue cells, as the collagen fluctuates between a state of semi-fluid to a rather stiff, stretchy substance depending on the nature of circumstances in the surrounding tissue.

This week, a group of researchers from Stanford discovered how collagen transitions between these two states, offering insight on how collagen networks can behave and respond to cellular interactions. This new information could enable scientists to encourage collagen growth in specific ways, including the potential to heal wounds or replace tissue.

"The extracellular matrix is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells within our tissues," says Ovijit Chaudhuri, assistant professor of mechanical engineering at Stanford and one of the lead authors on the work. "One of the key structural components of the extracellular matrix is collagen, and matrices of collagen exhibit remarkable mechanical properties. These complex mechanical behaviors are likely to be relevant to cellular interactions with these matrices."

Chaudhuri and his group began investigating some of these unique mechanical properties to see if they could promote regeneration in tissues affected by breast cancer. His group found that enhanced tissue stiffness actually promotes breast cancer progression, and conversely found that when the stiffness was altered, they could cue the stem cells to differentiate.

"We found that the strain stiffening behavior of these scaffolds or matrices is coupled with their liquid-like behavior: at greater deformations, these matrices become stiffer but then flow more rapidly to relax this increase in stiffness," Chaudhuri says. "As cells have been found to sense and respond to the mechanical properties of collagen matrices, it is likely that these complex mechanical behaviors in collagen networks are sensed by cells."

The new insights show that cell behaviors are deeply influenced by mechanical properties, which indicates that the specific mechanical properties of collagen could be vital in the process of regulating cell behavior. In other words, this new understanding of collagen's varying elasticity could have a significant impact on the area of regenerative medicine.

"By better understanding the fundamental mechanics of collagen networks, we can better design biomaterials that mimic certain aspects of these networks for regenerative medicine," Chaudhuri says.

Unlocking the secrets of regenerative medicine continues to be a hot trend in medical research, as doctors look for more effective methods of treatment. Just last fall, speaking at an MD&M event in Philadelphia, a Drexel University professor spoke about how exploring and understanding biomarkers like inflammation can lead to enhanced methods of wound healing and regenerative medicine.

As for Chaudhuri and his colleagues, they believe that this new understanding highlights how cells interact constantly with their microenvironments, and that collagen tends to affect those interactions with their elasticity and viscoelasticity. The hope is that with an increased understanding of interactions between cells and collagen, these new insights could help scientists develop new techniques for 3-D cell cultures, a better understanding of breast cancer progression, and possibly new methods for tissue regeneration. 

Kristopher Sturgis is a contributor to Qmed and MPMN.

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