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Gholami, Azam (2007): Actin-based motility. Dissertation, LMU München: Faculty of Physics
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Abstract

Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, move inside the infected cells by riding on an actin tail. The actin tail is formed from highly crosslinked polymerizing actin filaments, which undergo cycles of attachment and detachment to and from the surface of bacteria. In this thesis, we formulated a simple theoretical model of actin-based motility. The physical mechanism for our model is based on the load-dependent detachment rate, the load-dependent polymerization velocity, the restoring force of attached filaments, the pushing force of detached filaments and finally on the cross-linkage and/or entanglement of the filament network. We showed that attachment and detachment of filaments to the obstacle, as well as polymerization and cross-linking of the filaments lead to spontaneous oscillations in obstacle velocity. The velocity spike amplitudes and periods given by our model are in good agreement with those observed experimentally in Listeria. In this model, elasticity and curvature of the obstacle is not included. Future modelling will yield insight into the role of curvature and elasticity in the actin-based motility. As an important prerequisite for this model, we used analytical calculations as well as extensive Monte Carlo (MC) simulations to investigate the pushing force of detached filaments. The analysis starts with calculations of the entropic force exerted by a grafted semiflexible polymer on a rigid wall. The pushing force, which is purely entropic in origin, depends on the polymer's contour length, persistence length, orientation and eventually on the distance of the grafting point from the rigid wall. We checked the validity range of our analytical results by performing extensive Monte Carlo simulations. This was done for stiff, semiflexible and flexible filaments. In this analysis, the obstacle is always assumed to be a rigid wall. In the real experimental situations, the obstacle (such as membrane) is not rigid and performs thermal fluctuations. Further analytical calculations and MC simulations are necessary to include the elasticity of the obstacle