PHYSICAL INFRASTRUCT FOR CELL BIOLOGICAL MODELS CYTOSKELETAL FILAMENTS & MOTORS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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。细胞内细胞器沿微管(MT)和肌动蛋白细丝(AF)的运输是由肌球蛋白家族中相反极性的微管马达和肌动蛋白依赖马达驱动的。该模型包括两种颗粒运动模式，即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。最近发展起来的虚拟单元数学工作空间模拟定向输运的能力已被用于求解相应的扩散-平流-反应方程。该模型为研究信号对鱼类黑素细胞色素颗粒聚集和分散的影响提供了一种方便的工具。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，并做出了一些可以通过实验检验的预测

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 (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