442033 Integration of Cellular Structures Modulate Motility and Response to Applied Force

Monday, November 9, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Alexandra Cerny, Chemical and Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA

Muscular dystrophies are a class of genetic disorders that affect children and adults through the weakening and destruction of muscle tissue, including skeletal and cardiac muscle. This disease is caused by malfunctions within the nuclear force transduction network that cause structural defects within the cell. We have shown a preliminary link between the structural proteins emerin, lamin A and spectrin and the ability of the cell to deform and reform from strain. However, there has not been a rigorous quantification and correlation of protein level and mechanical response of cells. For a proper mechanical model, we need to consider the full structure of the protein networks and how this network influences mechanics. Here we investigate the individual effects of proteins within the force propagation network through multiple different mechanical assays. The stretching assay tests the cell’s ability to maintain its shape under strain caused by stretching the cells on a substrate. The effects of tensile strain on the movement and shape of the cell can also be measured using a micropillar assay. It has been found that cells with knocked down KASH-domains, which are the main connection between the nucleus and the cytoskeleton, are unable to move smoothly through the micropillars and often get stuck with the nucleus lagging at the back end of the cell. The mean squared displacement of the cells with the inhibited KASH-domain was less than that of the control cells. This decrease in motility suggests the role of a mechanically integrated nucleus in the viability of the cell. In performing this research, we hope to characterize the different effects of each protein within the force propagation network on cell viability such that targeted treatment can be given to the patients who experience the effects of cell mechanical malfunctions.

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