Physical parameters characterizing dysfunction of neuronal cargo transport caused by the dynein inhibitor ciliobrevin

Synaptic cargo transport by the motor proteins kinesin and dynein in the axons of hippocampal neurons was investigated using non-invasive measurement of transport force based on non-equilibrium statistical mechanics and extreme-value statistics on the maximum transport velocity. Although direct physical measurements such as force measurement using optical tweezers are difficult in a non-equilibrium intracellular environment, the proposed non-invasive estimations enabled enumerating force producing units (FPUs) carrying a cargo comprising the motor proteins generating force. The number of FPUs served as a barometer for the stable and long-distance transport by multiple motors, which was then used to quantify the extent of damage to axonal transport resulting from ciliobrevin, a dynein inhibitor. Our results show interrelationships among force, velocity, and the number of FPUs, precisely describing transport dysregulation. Such measures may help quantify the damage to axonal transport resulting from neuronal diseases including Alzheimer9s, Parkinson9s, and Huntington9s diseases in future.