| dc.description.abstract | Cells reside in complex physicochemical environments which provide forces acting as cues that influence the molecular physiology. However, the mechanisms and interactions between the various physical forces and the resultant downstream phenotype still have significant gaps in knowledge. This dissertation focuses on implementing tools and protocols to investigate how vascular cells respond to specific external forces and how these engineered approaches can facilitate new understanding. Three specific approaches and findings will be highlighted.
The first approach entails using engineered in vitro systems to study the interactions of two key physical forces in vascular health: shear stress and matrix stiffness. These vessel-chip systems allow for investigating often confounding variables, finding that matrix stiffness impedes the protective effect of shear stress on endothelial cells.
The second approach uses a tailored electrocultureware system to study how external electrical fields influence endothelial cell growth and biology. This work demonstrates that electric impulses accelerate proliferation and potentiate YAP activity.
The third approach establishes a pipeline for accessing subcellular biomechanics, that is, it is a protocol which provides the full mechanical properties of individual cells. Using combined Atomic Force Microscopy and Structure Illumination Super Resolution Microscopy, individual endothelial cells can be modeled, with applications to investigating physical changes in the context of aging.
Altogether the methods and approaches described here provide a foundation for studying how endothelial cells respond to physical stimuli, how external forces interact and result in biological phenomena, and whether mechanical shifts due to disease states can alter these processes from a physical perspective. Further understanding of cellular force transduction is facilitated by these interdisciplinary approaches. | |
