Effects of molecular motor parameters on vesicle translocation in dendritic spines

Determine the quantitative effects of varying myosin motor parameters—including the attachment rate α, detachment rate β, initial attachment position A, maximum extension before forced detachment B, spring constant k, and the numbers of available binding sites for up and down motors n_U and n_D—on the probability of vesicle translocation and on the mean first passage time through dendritic spines modeled as closed constrictions characterized by the confinement factor ζ; and identify which of these parameters are viable targets for neuronal control to modulate transport efficiency.

Background

Dendritic spines are narrow, closed intracellular compartments where vesicle transport is driven by molecular motors and strongly influenced by confinement-induced drag. Understanding how motor-level parameters shape transport outcomes (probability and timing of delivery to the postsynaptic density) is challenging experimentally due to the small scales and complex geometry involved.

The paper develops a simplified stochastic model linking vesicle velocity switching dynamics to individual myosin motor parameters. Despite providing model-based predictions, the authors explicitly note that, particularly in dendritic spines, the consequences of changes in molecular motor parameters on vesicle translocation times and probabilities had not been established, motivating the formulation of this problem.