PHYSICAL INFRASTRUCT FOR CELL BIOLOGICAL MODELS CYTOSKELETAL FILAMENTS & MOTORS

细胞生物模型的物理基础设施细胞骨架丝

• 批准号: 7722707
• 负责人: LESLIE M LOEW
• 金额: $ 1.38万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722707
• 关键词: Accounting; Actins; Behavior; Binding; Biological Models; Cells; Computer Retrieval of Information on Scientific Projects Database; Computer software; Cytoplasmic Granules; Cytoskeletal Filaments; Development; Diffusion; Equation; Family; Fishes; Funding; Goals; Grant; Institution; Mediating; Melanophores; Microfilaments; Microtubules; Modeling; Motor; Movement; Myosin ATPase; Organelles; Pattern; Pigments; Property; RNA; Reaction; Research; Research Personnel; Resources; Signal Transduction; Simulate; Source; Testing; United States National Institutes of Health; base; in vivo; model development; tool; trafficking; virtual

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该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沿细胞骨架细丝的运动。一种确定性的方法被用来模拟细胞内细胞器沿微管和肌动蛋白细丝的运输，它是由肌球蛋白家族的相反极性的MT马达和肌动蛋白依赖的马达驱动的。这一模型的发展推动了虚拟细胞软件的发展，以使用扩散-对流-反应方程来模拟定向传输。该模型现在被用作研究信号对鱼类黑素细胞中色素颗粒聚集和分散的影响的工具。第二个随机方法模型正在开发中，用于研究RNA颗粒在细胞中的运输，这主要是由基于微管的发动机驱动的。建立了具有两种相互竞争类型的多个电机的颗粒定量模型，并利用虚拟单元进行了数值模拟。基于单个电机的特性，考虑了颗粒非活动电机对主动电机施加阻力和主动电机对非主动电机施加拉力的相互影响。颗粒马达与微管的随机相互作用被建模，假设每个马达有三种可能的状态：未结合、结合但不活跃和活跃。该模型解释了在体内观察到的RNA颗粒行为的模式，并做出了一些可以在实验中检验的预测。