Understanding Morphogenesis with Biomaterials
Epithelium is the layer of tissue that covers most of the of internal and external surfaces of your body and organs, a wide-ranging inventory that includes the skin, lungs, gut, urinary and reproductive tracts. The process by which epithelia transforms into these things, epithelial morphogenesis, is critical in the construction and ongoing maintenance of your body, which includes tissue repair.
Playing an essential role in this transformation is the extracellular matrix (ECM), providing physical scaffolding for cells, but also initiating biophysical and biochemical cues required for morphogenesis – contributions that are poorly understood.
“We know morphogenesis is heavily influenced by the surrounding cell matrix, the ECM around the cells,” says Andrés J. García, faculty member of the Parker H. Petit Institute for Bioengineering and Bioscience. “But the ECM is very complex and difficult to study in its normal state.”
So García, Rae S. and Frank H. Neely Endowed Chair and Regent’s Professor in the Woodruff School of Mechanical Engineering, and his colleagues set out to develop a better understanding by making their own matrices, and published their research recently in The Journal of Cell Biology, a paper entitled, “Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis.”
The team engineered synthetic ECM-mimetic hydrogels to better study the impact of ECM properties on epithelial morphogenesis. Using synthetic matrices, the researchers could control mechanical properties and biochemical signals, making comparisons to a normal matrix.
“To me, the most remarkable thing was that we were able to find formulations that gave rise to normal structures, like you see in a normal matrix,” García says. “If we change the properties we could get conditions that did not allow the cells to grow. They basically stay a single cell and die. And then we had other conditions that gave rise to abnormal structures that looked like pathological conditions – all of this within the same material.”
In addition to elucidating the contributions of ECM biophysical and biochemical properties to morphogenesis, the research also provides a platform, García says, “that can be used to study the process. As a research tool it has a lot of value. If we want to engineer the matrices to direct cells during repair, this provides a good platform, because we’re not relying on matrix derived from the tumor of an animal. We can make it synthetically.”
Basically, it’s technology that can be used to answer fundamental questions of biology while also having a real impact in biomedical technologies, which ultimately leads to better treatments for patients.
García’s co-authors were fellow Petit Institute researcher Todd Sulchek, associate professor in the Woodruff School, as well as Ph.D. students, Ricardo Cruz‑Acuña, Tom Bongiorno, Christopher T. Johnson and José R. García, and the paper’s lead author, former Georgia Tech Ph.D. student Nduka O. Enemchukwu, now a postdoc at the Baylor School of Medicine.