Stochastic Modeling of the Behavior of Dynein

Abstract

Molecular motors are proteins that convert stored energy into physical work inside cells, and thus are the engines that drive many cellular functions. An individual motor can be studied using a laser trap to measure its response to working against an external force. Axonemal dynein is the molecular motor responsible for the rhythmic beating of eukaryotic cilia and flagella. An individual axonemal dynein molecule is capable of both unidirectional, processive motion and bidirectional motion when placed under a load (Shingyoji et al., 1998). This capability may be an important underlying factor in the mechanism for flagellar and ciliary motion. A detailed stochastic model is proposed which links the physical motion of a two-headed dynein molecule to the biochemical steps of its ATP hydrolysis cycle. Forward motion is driven by ATP hydrolysis, while backward motion is due to a passive process of biased diffusion. The model exhibits both processive and bidirectional behaviors. A simplified model which can be more easily analyzed is derived, as is an alternate version which steps backward actively, rather than sliding passively. The simplified models are then used to predict motor characteristics such as the load-velocity profile, the stall force, and the effective diffusion coefficient, which can be determined experimentally and used to distinguish among competing mechanisms.