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Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. In this study, we present theoretical arguments that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Our theoretical analysis suggests that this opposition to motion increases rapidly as the cargo approaches the wall. We find that having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus minimizes the effects of any opposition to transport. Even if microtubules are randomly placed in axons, we find that the higher density of microtubules found in small-caliber axons increases the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. The boundary effect is not a factor in transport in large-caliber axons where the microtubule density is lower.

Intra-cellular transport via the microtubule motors kinesin and dynein plays animportant role in maintaining cell structure and function. Often, multiple kinesinor dynein motors move the same cargo. Their collective function dependscritically on the single motors’ detachment kinetics under load. Single Kinesin’sand Dynein’s super-force off rates have been measured using anoptical-trap based method. We rapidly increased the force on a moving beadand measured the time to detachment. From such events, detachment time distributionsfor specific super-force values have been measured. In contrast toa possible constant off-rate kinesin has an off-rate increasing with force. Atlow loads, dynein is sensitive to load; detaching easily but at higher load it exhibiteda catch-bond type behavior, with off rate decreasing with load. Thesuper-force experiments also allowed us to determine the probability of backwardstepping for the motors. Kinesin and dynein can back-step under load, butthis was relatively rare in both directions (