Bimodality in a System of Active and Passive Kinesin-1 Motors

Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesin and dynein, work together to perform the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer and other neurodegenerative diseases. In particular two diseases, Hereditary Spastic Paraplegia (HSP) and Charcot-Marie-Tooth type 2A neuropathy (CMT2A) are connected to mutations of kinesin family members in the motor domain that affect their ATPase activity. However, it is not known how in detail multi-motor based cargo transport is impacted if the motor function of a fraction of motors is inhibited. In order to mimic hindered multi-motor transport in-vitro, we performed gliding motility assays with varying fractions of active kinesin-1 and passivated kinesin-1 (rigor mutants). We found that hindered gliding manifests in three motility regimes: gliding at the velocity of single motors, simultaneous gliding and stopping (bistable movement), and stopping. Notably, an abrupt transition from gliding to stopping occurred at a certain threshold fraction. Furthermore, we developed a theoretical description based on single motor parameters. Our model explains the bimodal microtubule movement as well as the sharp transition from gliding to stopping. Our results demonstrate that hindered transport is acting in a bimodal "either-or-fashion": depending on the fraction of passive motors, transport by a multi-motor system is either performed close to full speed or not at all.