Physical Nature of Cytoplasm

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Physical Nature of Cytoplasm

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Title: Physical Nature of Cytoplasm
Author: Guo, Ming
Citation: Guo, Ming. 2014. Physical Nature of Cytoplasm. Doctoral dissertation, Harvard University.
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Abstract: Forces are increasingly recognized as major regulators of cell physiology and function, and the mechanical properties of cells are essential to the mechanisms by which cells sense forces, transmit them to the cell interior or to other cells, and transduce them into chemical signals that impact a spectrum of cellular responses. Furthermore, cells can sense their extracellular environment and regulate their own mechanics and biology. Due to limitation of methodology, the cortical property of cells has been extensively characterized; however, the mechanics and dynamics of cytoplasm which consists all key cellular organelles, remains poorly understood. Moreover, a basic understanding of cell mechanics, such as which parameters correlates with cell stiffness and therefore impact cell biology is unknown. In this thesis, we firstly present a thorough investigation of the mechanical and dynamic properties of the cytoplasm, including direct measurement of cytoplasmic material property using optical tweezers, and visualization of intracellular dynamics by tracer particles. By combining these two measurements we obtain a directly characterization of the cytoplasmic forces; we further apply this method to study cancer cells and cells without vimentin intermediate filament, and find that cancer cells have significantly stronger intracellular forces, which vimentin intermediate filament does not have effect on the force generation. Secondly, we present our result on the role of cell volume in cell mechanics and cell biology. We show that the volume of a cell changes upon the property of the extracellular environment; the change in cell volume directly induces change in the mechanical property of both cytoplasm and cell cortex. We further show that the change in cell volume is due to intracellular water influx/efflux, and this has significant impact on cell biology, such as stem cell differentiation. Finally, we present a direct characterization of the equation of state of living cells by measuring cell volume under increasing osmotic pressure. We show that a living cell, under osmotic compression, behaves as Van der Waals gas with a hard sphere excluded volume; the minimum volume of cells is determined by cellular proteins, which the equation of state of living cells is dominated by intracellular ions.
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