M.S. Biomedical Engineering
Henry M. Rowan College of Engineering
Sebastián L. Vega, Ph.D.
Committee Member 1
Peter A. Galie, Ph.D.
Committee Member 2
James M. Holaska, Ph.D.
Adaptation, HAVDI, Mechanosensing, Stem cells, YAP
Mesenchymal stem cells; Colloids; Tissue engineering
Biomedical Engineering and Bioengineering
The goal of this research is to identify the role of engineered cell-cell signals on how cells sense material properties. Mesenchymal stem cells (MSCs) are adult cells whose behavior is regulated by matrix mechanosensing, which is characterized by stiffness-dependent changes in cell shape and the nuclear localization of mechano-transducer proteins including YAP (Yes-associated Protein). MSC area and nuclear YAP translocation increase with increasing stiffness, and although low levels of N-cadherin-based cell-cell signaling reduce this effect, two fundamental questions remain: (1) do engineered cell-cell signals at higher concentrations further reduce matrix mechanosensing, and (2) does N-cadherin signaling affect MSC adaptation to dynamic materials. To answer these questions, a stiffening hydrogel system was developed to independently control stiffness and HAVDI, a peptide that mimics cell-cell signaling. High concentrations of HAVDI (2 mM) reduce matrix mechanosensing on static hydrogels as seen by a decrease in area and nuclear YAP. The area of MSCs on soft HAVDI hydrogels that are stiffened does not change, but surprisingly nuclear YAP increases post-stiffening. These studies demonstrate that competing stiffness and cell-cell signals regulate matrix mechanosensing, and these insights are critical towards developing in vitro platforms to study ailments attributed to tissue stiffening including cancer, fibrosis, and aging.
Lowe, Matthew E., "EFFECTS OF CELL-CELL SIGNALING ON MESENCHYMAL STEM CELL MECHANOSENSING AND ADAPTATION TO DYNAMIC MATERIAL" (2022). Theses and Dissertations. 3056.