title: Multimotor transport in a system of active and inactive kinesin-1 motors.
abstract: 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 kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.
authors.affiliation: B CUBE - Center for Molecular Bioengineering, Technische Universität Dresden, Dresden, Germany; Max Planck Institute of Cell Biology and Genetics, Dresden, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Scharrel
authors.affiliation: Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.affiliation: B CUBE - Center for Molecular Bioengineering, Technische Universität Dresden, Dresden, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Max Planck Institute for the Physics of Complex Systems, Dresden, Germany. Electronic address: julicher@pks.mpg.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Jülicher
authors.affiliation: B CUBE - Center for Molecular Bioengineering, Technische Universität Dresden, Dresden, Germany; Max Planck Institute of Cell Biology and Genetics, Dresden, Germany. Electronic address: diez@bcube-dresden.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Diez
mesh_terms: D001370:Axonal Transport; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009038:Motion; D009154:Mutation; D013269:Stochastic Processes
chemical_list: D016547:Kinesins