(623g) A Multi-Scale Model For Actin-Based Propulsion Of Invasive Bacteria And Other Intracellular Particles

Invasive pathogens (such as Listeria monocytogenes) and other intracellular particles can be propelled by actin polymerization from the particle surface. Propulsion requires particles to be coated with filament-nucleation protein factors, such as Listeria's ActA, N-WASP (neural Wiskott-Aldrich Syndrome Protein), or the N-WASP VCA domain, which catalyze the polymerization of actin filaments from the particle surface to generate a densely cross-linked F-actin ?rocket tail?, which thrusts the particle forward when anchored to the host cell cytoskeleton. There is increasing evidence that these surface-bound factors (ActA by its interaction with Vasodilator-Stimulated Phosphoprotein or VASP) also act as ?filament end-tracking motors?, which facilitate (+)-end assembly and force generation by linking the elongating filament end to the particle surface and processively inserting new actin monomers, as we originally argued (Dickinson & Purich, Biophys J, 85:605-617 2002). Here we present a multi-scale three-dimensional reaction/diffusion/mechanical model for actin-based particle propulsion, accounting for probabilistic monomer addition by end-tracking motors, mechanics of the hundreds of filaments interacting with the particle surface, and the spatial monomer concentrations gradients created by the rapid consumption of actin monomers at filament ends. This model can predict and explain several puzzling and interesting characteristics of particle propulsion that have been reported experimentally, including rotating and helical particle trajectories, tubular rocket tails, episodes of monomer-sized steps, larger scale saltatory motion (when filaments are more weakly bound), and an inverse relationship between filament density and particle speed. That these characteristics all arise naturally from the filament-end tracking mechanism with very few complicating assumptions gives additional support to the end-tracking motor hypothesis.