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Title: Mechanics of Cell Growth
Authors: Feric, Marina
Advisors: Brangwynne, Clifford P
Contributors: Chemical and Biological Engineering Department
Keywords: Cell size
Liquid droplets
Nuclear actin
Subjects: Chemical engineering
Cellular biology
Issue Date: 2016
Publisher: Princeton, NJ : Princeton University
Abstract: Organisms vary in size by orders of magnitude spanning 1 μm to hundreds of meters, yet their cells remain on the micron length scale. The physical mechanisms that control the size of cells remain unclear. Here, I study the extraordinarily large oocytes (immature eggs) from the frog Xenopus laevis to understand how cell organization and mechanics change as these cells grow to reach sizes of 1 mm. I discover that these oocytes have evolved to contain a unique nuclear actin meshwork that supports the liquid-like nuclear bodies from gravitational sedimentation and mass fusion events. I find that gravitational forces on organelles dominate random thermal forces for cell sizes greater than ~100 μm, suggesting that large cells require novel mechanisms to maintain proper spatial organization. Directly probing the material properties with active microrheology, I find that nuclear actin forms a soft viscoelastic network that is capable of undergoing gravitational creep on the time scale of growth. This suggests that the material properties of nuclear actin are matched to its mechanical role in kinetically stabilizing an emulsion of nuclear bodies during growth. For forces higher than 1 g and for longer times, these nuclear bodies will undergo significant displacements in the nucleus due to gravitational creep, thereby disrupting proper cellular organization. Although these nuclear bodies are known to behave as liquids, it still remains unknown how they maintain three distinct compartments. Visualizing nuclear actin shows protrusion of filaments inside these nuclear bodies in between different compartments, and by disrupting nuclear actin, I find that these compartments are able to rearrange and undergo homotypic fusion events. In combination with in vitro approaches, I determine that each nucleolar compartment represents a distinct liquid-like phase, and these nuclear bodies are thus behaving as multiphase droplets. Principles from liquid-liquid phase transitions provide a physical framework for organization even within organelles. Overall, X. laevis oocytes are an example of how cells can evolve to reach large sizes. Simple biophysical mechanisms can allow cells to maintain structural organization, even on length scales ~1,000 times their typical size.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemical and Biological Engineering

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