"As bioengineers, we can now design 3D culture systems where environmental parameters such as composition, porosity, and stiffness can be precisely tuned to study the importance of these cues on tumorigenesis," says coauthor Sandeep Koshy, a Harvard graduate student in the Harvard-MIT Program in Health Sciences and Technology, who works in Mooney's lab at Harvard SEAS and at the Wyss Institute for Biologically Inspired Engineering. "We're seeing that some of these factors have a major impact on cell behavior that is not possible to observe in conventional 2D cell cultures."
Prior studies have used varying amounts of a fibrous protein called collagen to adjust the stiffness of the extracellular matrix, but Mooney's team recognized early on that collagen has more than a simple mechanical effect on cells: it can also trigger certain signaling pathways. Fibrous collagen is not normally found in the basement membrane that surrounds the mammary epithelium, so any collagen signaling could confound the conclusions of those studies.
To eliminate uncontrolled variables, the team designed a new material model that uses alginate gel, instead of collagen, to stiffen the extracellular matrix without binding to any cell receptors. When this model was in its softest mode, normal (benign) mammary epithelial cells behaved normally within it, forming cellular structures referred to as acini that capture many key features of the normal in vivo mammary epithelium. But when the gel was stiffer, the cells began to upregulate the expression of cancer-
|Contact: Caroline Perry|