Within living cells, actin polymerization propels endosomes, phagosomes, some viruses, and several types of invasive bacteria, including Listeria, Shigella, Rickettsia, and Burkholderia. In each of these cases, the surface of the propelled particle mimics the cell membrane molecular components required for the nucleation and polymerization of actin filaments in the formation of cell protrusions. A key protein involved in this process is the neuronal Wiskott-Aldrich Sydrome Protein (N-WASP), or closely related proteins (such as VASP) and bacterial mimics to N-WASP (e.g., BimA on Burkholderia and RickA on Rickettsia). We hypothesize these proteins act as filament end-tracking motors, linking the elongating filament plus-end to the particle surface and capturing energy from ATP hydrolysis for processive plus-end assembly of the actin filament. This presentation covers the predicted kinetic and thermodynamic properties of actin filament end-tracking motors (‘actoclampins’) and how these properties explain several different observations of actin-based motility of hard and soft particles. To relate particle transport properties to molecular motor kinetics, we employ probabilistic protein-scale modeling, filament-scale modeling of local network mechanics, and continuum reaction-diffusion-mechanical modeling on the particle length scale to predict particle speed and dynamic deformations.
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