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: 7366488
• 负责人: LESLIE M LOEW
• 金额: $ 5.11万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7366488
• 关键词: PHYSICAL; INFRASTRUCT; CELL; BIOLOGICAL; MODELS

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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该项目的目标是创建必要的物理和计算表示，以有效地模拟沿细胞骨架细丝的细胞内运动。建立了一种确定性的方法来模拟细胞内细胞器沿微管（MT）和肌动蛋白丝（AF）的运输，这是由肌凝蛋白家族的反极性MT马达和肌动蛋白依赖马达驱动的。该模型包括颗粒运动的两种模式，mt相关的定向运动和af相关的随机行走，以及在这些模式之间的切换。最近开发的虚拟单元数学工作空间模拟定向输运的能力被用来求解相应的扩散-平流-反应方程。该模型为研究信号对鱼类黑色素细胞中色素颗粒聚集和分散的影响提供了便利的工具。本文建立了具有两种竞争类型的多个电机的颗粒的定量模型，并用虚拟单元进行了数值模拟。在单电机特性的基础上，考虑了它们之间的相互影响，以颗粒为中介，非活动电机对主动电机施加阻力，主动电机对非活动电机施加拉力。对颗粒马达与微管的随机相互作用进行了建模，假设每个马达有三种可能的状态：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颗粒行为模式，并做出了一些可以进行实验验证的预测