Intranuclear strain measured by iterative warping in cells under mechanical and osmotic stress
Date of Award
Doctor of Philosophy (PhD)
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The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of cells embedded in their native extracellular environment. Therefore, a hybrid imaging and model based image registration technique has been developed to enabled us to explore links between biomechanical and biochemical signaling within individual cells. The hybrid technique uses an iterative warping deformable image registration to measure intranuclear strain fields that are correlated to nuclear structures. Three cell mechanics methods were developed to examine the mechanical response of the nucleus under different mechanical conditions. 1) Strain transfer from tissue to nuclei in a cartilage tissue deformation model paired with nascent RNA expression, 2) strain transfer to the nucleus with different cell types on a stretchable membrane, and 3) force traction microscopy of cells during osmotic stress. Intranuclear strain fields provide spatial details of the nucleus that when paired with single cell biochemical assays will provide insight into how mechanical forces transferred to the nucleus influence gene expression.
Henderson, Jonathan T, "Intranuclear strain measured by iterative warping in cells under mechanical and osmotic stress" (2014). Open Access Dissertations. 283.
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