The three-dimensional microenvironment surrounding cells of the mammary glands profoundly influences the progression of breast cancer. Given the dynamic and interactive components of the extracellular matrix (ECM), understanding the interplay between ECM behavior and morphogenetic programs requires the development of a controllable and tunable lab platform.
In a new study published in Science Advances titled, “Engineered basement membrane mimetic hydrogels to study mammary epithelial morphogenesis and invasion,” researchers from the University of California, Santa Barbara (UCSB) led by Ryan Stowers, PhD, assistant professor of mechanical engineering, have created an algae-based gel that successfully supports the development of normal mammary gland tissue and can be modified to direct how cells grow. By adjusting the mechanical and biochemical properties of the gel, researchers can learn more about how cells in the body are shaped by their physical environment.
“Not only did we create something that can mimic commercially made gels, but we were able to use what we’ve made to our advantage to learn more about the cells and the material,” said Jane Baude, graduate student in the Stowers lab and first author of the study.
“The environment the cell grows in is just as important as its genetics,” said Stowers. “You can put the same cells in different environments and they might behave like normal cells, or they might behave like invasive malignant cells, just by changing the context that they’re growing in.”
As cells respond to the physical properties of their surroundings, adjusting these properties in the lab can allow researchers to evaluate cell behavior in environments with varying mechanoproperties. Recent research has linked stiffer surrounding environments to tumor development.
“Oftentimes, when people feel a stiff lump, they go get it checked out, knowing intuitively that this hard mass, this stiff lump, is potentially bad,” Stowers explained. “The mammary gland is one of the softer tissues in the body, but a malignant tumor actually increases in stiffness as disease progresses.”
To develop the synthetic basement membrane, Baude used a previously studied algae-based gel and tested combinations of short peptide sequences until it matched the capabilities of Matrigel, a commercially available gel for studying mammary cells. The authors varied the crosslinking and length of polymer chains in the gel to modify its stiffness and how quickly it responds to applied force.
“We found a combination of mechanical and biochemical cues that work well,” said Baude. “Some of the changes we were able to make in the gel help us pick apart how different kinds of matrices contribute to cell development.”
Stowers and his colleagues are interested in exploring the extent to which they can control the initial conditions of the gel to shape cell development, including the possibility of using the gel to grow complex tissues and organs from patient cells.
“We’re hopeful,” he said, “that by applying an engineering approach to developmental biology, we can uncover insights into how to guide the formation of complex, functional engineered tissues.”