title: Axonal transport: how high microtubule density can compensate for boundary effects in small-caliber axons.
abstract: 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.
authors.affiliation: Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Wortman
authors.affiliation: Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697.
authors.forename: Uttam M
authors.initials: UM
authors.lastname: Shrestha
authors.affiliation: Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Barry
authors.affiliation: Biological Sciences, University of Missouri, Columbia, MO 65211.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.affiliation: Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697. Electronic address: cyu@uci.edu.
authors.forename: Clare C
authors.initials: CC
authors.lastname: Yu
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008959:Models, Neurological
chemical_list: D016547:Kinesins