Browsing by Author "Uppulury, Karthik"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Analysis of Cooperative Behavior in Multiple Kinesins Motor Protein Transport by Varying Structural and Chemical Properties
    (Springer, 2013) Uppulury, Karthik; Efremov, Artem K.; Driver, Jonathan W.; Jamison, D. Kenneth; Diehl, Michael R.; Kolomeisky, Anatoly B.
    Intracellular transport is a fundamental biological process during which cellular materials are driven by enzymatic molecules called motor proteins. Recent optical trapping experiments and theoretical analysis have uncovered many features of cargo transport by multiple kinesin motor protein molecules under applied loads. These studies suggest that kinesins cooperate negatively under typical transport conditions, although some productive cooperation could be achieved under higher applied loads. However, the microscopic origins of this complex behavior are still not well understood. Using a discrete-state stochastic approach we analyze factors that affect the cooperativity among kinesin motors during cargo transport. Kinesin cooperation is shown to be largely unaffected by the structural and mechanical parameters of a multiple motor complex connected to a cargo, but much more sensitive to biochemical parameters affecting motor-filament affinities. While such behavior suggests the net negative cooperative responses of kinesins will persist across a relatively wide range of cargo types, it is also shown that the rates with which cargo velocities relax in time upon force perturbations are influenced by structural factors that affect the free energies of and load distributions within a multiple kinesin complex. The implications of these later results on transport phenomena where loads change temporally, as in the case of bidirectional transport, are discussed.
  • Thumbnail Image
    Item
    Cooperative mechanisms in coupled motor proteins transport
    (2012) Uppulury, Karthik; Kolomeisky, Anatoly B.
    Subcellular cargos are transported by enzyme molecules called molecular motors by using the chemical energy from hydrolysis of ATP and performing mechanical work in non-equilibrium. Certain motors tread on cytoskeleton structures i.e. microtubules and actin filaments in a linear manner. Due to the polarity of the cytoskeleton structures the motors can accomplish cellular transport along one direction. Cargos often rely upon the collective action of more than one motor to transport them in order to surmount the crowding and visco-elastic effects of the surrounding medium through higher force generation. To understand the mechanism of cargo transport by precisely two kinesin-1 motors a combination of experimental and theoretical approaches were employed. This thesis focuses on understanding the mechanism of transport by considering interactions between closely spaced motors on the microtubules. The main finding of this thesis is that motors under the influence of each other's interaction with microtubules do affect the cargo dynamics.
  • Thumbnail Image
    Item
    How the interplay between mechanical and non-mechanical interactions affects multiple kinesin dynamics
    (American Chemical Society, 2012) Uppulury, Karthik; Efremov, Artem K.; Driver, Jonathan W.; Jamison, D. Kenneth; Diehl, Michael R.; Kolomeisky, Anatoly B.
    Intracellular transport is supported by enzymes called motor proteins that are often coupled to the same cargo and function collectively. Recent experiments and theoretical advances have been able to explain certain behaviors of multiple motor systems by elucidating how unequal load sharing between coupled motors changes how they bind, step, and detach. However, non-mechanical interactions are typically overlooked despite several studies suggesting that microtubule-bound kinesins interact locally via short-range non-mechanical potentials. This work develops a new stochastic model to explore how these types of interactions influence multiple kinesin functions in addition to mechanical coupling. Non-mechanical interactions are assumed to affect kinesin mechanochemistry only when the motors are separated by less than three microtubule lattice sites, and it is shown that relatively weak interaction energies (~2 kBT) can have an appreciable influence over collective motor velocities and detachment rates. In agreement with optical trapping experiments on structurally-defined kinesin complexes, the model predicts that these effects primarily occur when cargos are transported against loads exceeding single-kinesin stalling forces. Overall, these results highlight the inter-dependent nature of factors influencing collective motor functions, namely, that the way the bound configuration of a multiple motor system evolves under load determines how local non-mechanical interactions influence motor cooperation.