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Mechanics of the nucleus in differentially uncommitted cells

Posted on:2011-02-04Degree:Ph.DType:Dissertation
University:Carnegie Mellon UniversityCandidate:Soares dos Santos Ribeiro, Alexandre JoseFull Text:PDF
GTID:1444390002961628Subject:Biophysics
Abstract/Summary:
When present, the nucleus occupies a large volume of the cell and its structures play a strong role in nuclear and cell mechanics. Mechanical properties are pivotal for cells to sense and internalize external forces, which may lead to alteration of function. Evidence suggests that function of differentially uncommitted cell types---cancer and stem cells---may be correlated to mechanics. Differentially uncommitted cells present the ability to differentiate, or transform in the case of cancer, the potential to invade tissues, away from their original niches, or tumors in the case of cancer, and present very similar organizations of chromatin and lamina structures. The aim here is to address how cell mechanics correlates to the functions of differentially uncommitted cells. We mechanically characterized 3 cancer cell models with micropipette aspiration---fibrosarcoma and melanoma lines---and 3 stem cell models---hematopoietic, mesenchymal and perivascular stem cells. In the fibrosarcoma, the variation of expression in one oncogene was enough to generate drastic alterations in structure and mechanics of the nucleus, while two melanoma cell lines in very different stages of transformation presented considerably different mechanical reactions to aspiration associated with different nuclear morphologies. Mechanics seems to vary considerably among stem cells with different origins and culture conditions, where different applications may be more efficient with specific stem cell types relatively to others based on mechanical properties. This study was associated with the analysis of nuclear and cytoplasmic structures, where special attention was given to A-type lamins as a possible component to be manipulated in order to tune nuclear and consequently cell mechanics. Structural changes were observed and analyzed in HeLa cells after regulating the expression and altering specific molecular properties of A-type lamins. Lamin ADelta50---a mutated form of A-type lamins---was expressed in metastatic melanoma cells and nuclear deformation was considerably reduced. Mechanics of the nucleus seems to play a strong role in defining the properties of differentially uncommitted cells. However, different mechanisms of nuclear mechanics were observed among the tested cells, suggesting the existence of more possible scenarios of structural organization in other differentially uncommitted cells.
Keywords/Search Tags:Cell, Mechanics, Nucleus, Nuclear
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