A Coarse-Grained Computational Model of Kinesin-Microtubule Gliding Assays on Lipid Bilayers

Vandal, Steven R.

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A Coarse-Grained Computational Model of Kinesin-Microtubule Gliding Assays on Lipid Bilayers

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Cytoskeletal filaments and their associated motor proteins play key roles in many cellular processes including cell division, locomotion, and cargo transport. One type of cytoskeletal filament, the microtubule, acts as the rigid structural skeleton of eukaryotic cells and forms the spindle during mitosis. Kinesin, a motor protein associated with the microtubule, processively steps along the microtubule hand-over-hand to transport cargo and to reorganize the microtubule network structure. Much has been done in recent years to characterize the biophysical properties of these proteins, and one of the most common methods is the gliding assay, performed on glass surfaces. Motors in vivo are often embedded in the plasma membrane or lipid vesicles, however, in which they can diffuse. This leads to quantitative and qualitative differences in behavior that are not reproduced in glass gliding assays. Here, we study the diffusion of kinesin-1 motors across a lipid bilayer and their accumulation onto microtubules using coarse-grained computer simulations. By comparing the resulting behavior to gliding assay experiments performed on a lipid bilayer, we can determine the on-rate of the motors onto the microtubule under biologically relevant conditions, and also shed light into finite size effects as well as the limit of the mean-field approach. We also develop a model for relating the velocity of the microtubule to the various mechanistic properties of the simulation, which agrees with both the high- and low-density regimes.

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