| Summary: | The heavily cross-linked microtubule (MT) bundles found in neuronalprocesses play a central role in the initiation, growth andmaturation of axons and dendrites; however, a quantitativeunderstanding of their mechanical function is still lacking. We heredeveloped computer simulations to investigate the dynamics of forcegeneration in 1D bundles of MTs that are cross-linked and powered bymolecular motors. The motion of filaments and the forces they exertare investigated as a function of the motor type (unipolar orbipolar), MT density and length, applied load, and motorconnectivity. We demonstrate that only unipolar motors (e.g.,kinesin-1) can provide the driving force for bundle expansion, whilebipolar motors (e.g., kinesin-5) oppose it. The force generationcapacity of the bundles is shown to depend sharply on the fractionof unipolar motors due to a percolation transition that must occurin the bundle. Scaling laws between bundle length, force, MT lengthand motor fraction are presented. In addition, we investigate thedynamics of growth in the presence of a constant influx of MTs.Beyond a short equilibration period, the bundles grow linearly intime. In this growth regime, the bundle extends as one mass forwardwith most filaments sliding with the growth velocity. The growthvelocity is shown to be dictated by the inward flux of MTs, toinversely scale with the load and to be independent of the freevelocity of the motors. These findings provide importantmolecular-level insights into the mechanical function of the MTcytoskeleton in normal axon growth and regeneration afterinjury.
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