UNIVERSITY PARK, Pa. — Esther Gomez, Waltemeyer Mid-Career Biotechnology Professor of Chemical Engineering at Penn State, has been awarded a five-year, $1.9 million Maximizing Investigators’ Research Award (MIRA) to study the mechanical properties of tissues and their impact on cell fate, the term for whether a cell grows, dies or transitions to another cell type. The results of the work could have implications for tissue development and understanding the progression of diseases like cancer and fibrosis.
MIRA is awarded through the National Institutes of Health (NIH)’s National Institute of General Medical Sciences.
Gomez’s lab studies how the physical properties of the extracellular matrix, the network of proteins that surround cells, impact the functional state of cells. Gomez and her group will use the award to investigate factors that regulate epithelial-mesenchymal plasticity, or the ability for cells to shift between states. Epithelial cells, which form tissues such as the lung, kidney and mammary gland, can lose some of their properties that allow them to remain stationary and grouped with like cells. They can become motile mesenchymal-like cells, which can migrate in the body and assist with repairing or reshaping tissues. This shift in cell state can help organs develop and wounds heal, but problems can arise when the process becomes dysregulated, contributing to diseases such as fibrosis and cancer.
“The chemical and mechanical properties of tissues help guide cells to perform specialized functions,” Gomez said, who also has a courtesy appointment in biomedical engineering. “During disease progression, the properties of a cell’s surrounding environment can change. We aim to better understand how cells sense and respond to these changes.”
For example, fibrosis can arise from accumulation of stiff scar tissue that forms as a tissue heals from injury or chronic inflammation. Excess scarring can impair the function of organs. Gomez also pointed to breast cancer as an example of how tissues change during disease progression, explaining that normal mammary tissue is softer than tumor tissue. The increased stiffness of tumors may promote the spread of cancer cells in the body and reduce the efficacy of cancer treatments.
Gomez’s team is building models of tissues that mimic the viscoelastic properties of the cell’s surroundings to investigate how the stiffness and time-dependent responses of tissues to mechanical forces impact epithelial-mesenchymal plasticity.
“This transition for cells is not a binary process, it is more of a spectrum: Cells can have both epithelial and mesenchymal features,” Gomez said. “In addition, similar cells can respond differently to the same signals resulting in a heterogenous cell population.”
Cellular heterogeneity can make it challenging to diagnose diseases and can have negative impacts on the success of treatment approaches.
Gomez said research into how mechanical properties of tissues impact cell state and heterogeneity may provide a better understanding of tissue development and disease progression — and contribute to advancements in therapeutics.
“The research can also provide information about which tissue properties are important for helping epithelial cells perform their specialized functions,” Gomez said. “This could help define design rules for engineering epithelial tissues for regenerative medicine.”
This research is supported by the National Institutes of Health’s National Institute of General Medical Sciences under award number 1R35GM163932-01. This content is solely the responsibility of the authors and does not necessarily represent the views of the funders.
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