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Phase transitions in the cell cytoplasm: a theoretical investigation

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Title: Phase transitions in the cell cytoplasm: a theoretical investigation
Authors: Wurtz, Jean-David
Item Type: Thesis or dissertation
Abstract: Biological cells organise their interior into compartments called organelles in order to function. The familiar ones are the mitochondria, the Golgi apparatus and the lysosomes, which are surrounded by a lipid membrane. There are also membrane-less organelles that are currently receiving intense attention from the biology and physics communities. Membrane-less organelles are ubiquitously present, from yeast cells to mammalian cells, and play key roles in biological functions. One of these are the stress granules (SG) that form in the cytoplasm when the cell is under stress, and are indispensable to the cell’s survival. Membrane-less organelles are proteinaceous liquid drops that assemble by phase separation in the cytoplasm. Phase separation under non-equilibrium conditions in the cell cytoplasm is poorly understood as a physical phenomenon, limiting our understanding of membrane-less organelles. In this thesis, we investigate the physics of non-equilibrium phase separation. Specifically, we study a ternary fluid model in which phase-separating proteins can be converted into soluble proteins, and vice versa, via ATP-driven chemical reactions. We elucidate using analytical and simulation methods how drop size, formation and coarsening are controlled by the reaction rates, and categorize comprehensively the qualitative behaviour of the system into distinct regimes. We then apply our formalism to SG formation. Guided by experimental observations, we consider minimal models of SG formation based on phase separation regulated by ATP-driven chemical reactions. We also provide specific predictions that can be tested experimentally. The model studied in this thesis is a minimal model of membrane-less organelle regulation in the cytoplasm, and can also be applied to chemically-controlled drops in emulsions in the engineering setting.
Content Version: Open Access
Issue Date: Sep-2017
Date Awarded: Mar-2018
URI: http://hdl.handle.net/10044/1/58857
DOI: https://doi.org/10.25560/58857
Supervisor: Lee, Chiu Fan
Department: Bioengineering
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Bioengineering PhD theses

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