PHYSICAL INFRASTRUCT FOR CELL BIOLOGICAL MODELS CYTOSKELETAL FILAMENTS & MOTORS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这个项目的目标是创建必要的物理和计算表示，以有效地模拟细胞内运动沿着细胞骨架丝。一种确定性的方法已经被开发用于模拟细胞器沿沿着微管和肌动蛋白丝的运输，这是由相反极性的MT马达和肌动蛋白依赖性马达的肌球蛋白家族驱动的。该模型的开发推动了虚拟细胞软件的开发，以使用扩散-平流-反应方程来模拟定向运输。该模型现在作为一种工具，用于研究信号对鱼类黑色素细胞中色素颗粒的聚集和分散的影响。第二个随机方法模型正在开发中，以研究RNA颗粒在细胞中的运输，这主要是由基于微管的马达驱动。 一个定量模型的颗粒与两个竞争类型的多个电机已制定和数值模拟使用虚拟细胞。根据单个马达的特性，考虑了颗粒非活动马达对活动马达施加阻力，活动马达对非活动马达施加拉力的相互影响。随机相互作用的颗粒电机与微管建模假设三种可能的状态，每个电机未绑定，绑定，但不活跃和活跃。该模型解释了在体内观察到的RNA颗粒行为的模式，并做出了一些可以通过实验验证的预测。

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 and actin filaments, which is driven by opposite-polarity MT motors and actin-dependent motors of myosin family. Development of this model drove the development of the Virtual Cell software to model directed transport using diffusion-advection-reaction equations. The model now serves as a tool for studying the effect of signaling on aggregation and dispersion of pigment granules in fish melanophores. A second stochastic approach model is being developed to study RNA granule trafficking in cells, which is driven primarily by microtubule-based motors. 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 experimentally.