Endocytosis is a process by which cells bring external materials into the intracellular environment and perform other essential biological functions. The main drivers of endocytosis include clathrin and actin, which help shape the membrane and form the endocytic invagination. In mammalian cells and other cells lacking a wall, the primary barriers to endocytosis are the bending rigidity of the cell membrane and surface tension. However, in cells with a rigid cell wall, such as those of yeast, this process is opposed by a substantial pressure within the cell, known as the turgor pressure, which is generated by a difference in the concentration of osmolytes such as glycerol across the membrane. In order to understand yeast endocytosis, it is necessary to understand how force and curvature generators behave under conditions of high turgor pressure, as well as other possible mechanisms cells may employ to reduce or overcome the turgor pressure barrier.
In this thesis, we model the generation of these high turgor pressures through osmolyte diffusion and accumulation, as well as examining the production of forces by curvature-generating molecules (CGMs) under high turgor pressure. We first investigate the possibility of reducing the turgor pressure barrier to endocytosis by modeling the steady-state reduction of the glycerol concentration, and thus the turgor pressure, in a cell with a single region of increased permeability, corresponding to a cell with a single endocytic zone. We then extend this model to cells with multiple endocytic zones, as well as to the time dependence of the glycerol concentration. We also model the behavior of idealized curvature-generating molecules under high-turgor pressure conditions in the presence of a stiff cell wall. We find that small numbers of channels can produce up to a 50% reduction in the turgor pressure. We also find that model CGMs analogous to clathrin can produce forces nearly sufficient to overcome the turgor pressure.
|Advisor:||Carlsson, Anders E|
|Commitee:||Bayly, Philip, Mukherji, Shankar, Nussinov, Zohar, Wessel, Ralf|
|School:||Washington University in St. Louis|
|School Location:||United States -- Missouri|
|Source:||DAI-B 81/4(E), Dissertation Abstracts International|
|Keywords:||CGP, diffusion, glycerol, Helfrich energy, theoretical, yeast|
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