Actin-based motility

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