Stochastic Simulations of Tropomyosin Binding and Diffusion on Filamentous Actin

Abstract

The actin-binding protein tropomyosin plays a key role in regulating both the interaction of filamentous actin (F-actin) with other binding proteins, as well as the bending rigidity and biochemistry of F-actin itself. Tropomyosin binds to F-actin in a 1:7 ratio, with one tropomyosin unit covering 7 actin monomers. Tropomyosin units can form end-to-end bonds with their neighbors, and have been experimentally observed to nucleate and form tropomyosin chains on the actin filament, which can elongate and decorate the actin filament. However, since tropomyosin spans 7 actin monomers, two such tropomyosin chains on the same actin filament have a 6-in-7 chance of being out of register, leaving a gap in decoration of one or more actin monomers where they meet. Lateral diffusion of tropomyosin chains on F-actin was recently proposed as a potential mechanism by which gaps in decoration could be resolved. Here, we present stochastic computer simulations of tropomyosin binding to F-actin. We develop a theoretical framework based on the hydrodynamic drag experienced by tropomyosin during diffusion, and simulate tropomyosin's decoration to F-actin and the development and resolution of gaps in decoration over time. Our results support lateral tropomyosin diffusion on F-actin as a potentially essentially mechanism by which tropomyosin molecules can decorate filamentous actin without leaving gaps in decoration.