PHYSICAL INFRASTRUCT FOR CELL BIOLOGICAL MODELS CYTOSKELETAL FILAMENTS & MOTORS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to create the necessary physical and computational representations to effectively model intracellular movement along cytoskeletal filaments. A deterministic approach has been developed for modeling the intracellular organelle transport along microtubules (MT) and actin filaments (AF) which is driven by opposite-polarity MT motors and actin-dependent motors of myosin family. The model includes two modes of granule movement, MT-associated directed motion and AF-associated random walks, as well as switching between these modes. The recently developed capability of the Virtual Cell math workspace to model directed transport has been used to solve the corresponding diffusion-advection-reaction equations. The model proved to be a convenient tool for studying the effect of signaling on aggregation and dispersion of pigment granules in fish melanophores. A quantitative model of a granule with multiple motors of two competing types has been formulated and numerically simulated using the Virtual Cell. Based on the properties of single motors, it takes into account their mutual influence mediated by the granule inactive motors exert drag on active motors and active motors exert pull on inactive motors. Stochastic interaction of granule motors with the microtubule is modeled assuming three possible states for each motor unbound, bound but inactive and active. The model explains the patterns of RNA granule behavior observed in vivo and makes some predictions that can be tested experimentall