Computational model of dynein-dependent self-organization of microtubule asters
Computational model of dynein-dependent self-organization of microtubule asters
复制标题
DOI：
10.1242/jcs.00919
复制
发表时间：
2004-03-15
影响因子：
4
通讯作者：
Mogilner, A
中科院分区：
文献类型：
--
作者：
Cytrynbaum, EN;Rodionov, V;Mogilner, A
微管的极性排列;在细胞中起许多重要作用。通常，这样的阵列是由一个中心体组织的，中心体锚定微管的负端，而正端延伸到细胞周边。然而，分子马达和微管的集合也展示了自组织成极性阵列的能力。我们使用定量建模来分析的自组织微管星状体和电机驱动的色素颗粒的聚集在鱼黑素细胞片段。该模型是基于观察，微管是不动的，并与颗粒相关的细胞质动力蛋白电机的实验证据，有能力成核MT和衰减他们的负端动力学。该模型解释了观察到的事件序列如下。最初，由细胞质动力蛋白马达驱动的色素颗粒聚集到局部微管负端簇。然后色素聚集体使微管成核，微管的正端向片段边界生长，而负端暂时留在聚集体中。从一个聚集体中出现的微管与它们遇到的任何聚集体竞争，导致逐渐形成单个聚集体。同时，正反馈机制驱动单个MT星形的形成-单个松散聚集体导致集中的MT成核，因此更紧密的聚集体更有效地稳定MT负末端，从而导致星形形成。我们将基于实验测量的模型假设转化为数学方程。模型分析和计算机模拟成功地再现了所观察到的色素聚集和微管自组织的途径。我们通过观察各种大小的片段和双叶片段的自组织来测试模型预测。该模型提供了严格的限制率和浓度描述微管和电机动力学，并揭示了聚合物动力学和聚合物电机相互作用在细胞骨架组织的作用。
Polar arrays of microtubules; play many important roles in the cell. Normally, such arrays are organized by a centrosome anchoring the minus ends of the microtubules, while the plus ends extend to the cell periphery. However, ensembles of molecular motors and microtubules also demonstrate the ability to self-organize into polar arrays. We use quantitative modeling to analyze the self-organization of microtubule asters and the aggregation of motor-driven pigment granules in fragments of fish melanophore cells. The model is based on the observation that microtubules are immobile and treadmilling, and on the experimental evidence that cytoplasmic dynein motors associated with granules have the ability to nucleate MTs and attenuate their minus-end dynamics. The model explains the observed sequence of events as follows. Initially, pigment granules driven by cytoplasmic dynein motors aggregate to local clusters of microtubule minus ends. The pigment aggregates then nucleate microtubules with plus ends growing toward the fragment boundary, while the minus ends stay transiently in the aggregates. Microtubules emerging from one aggregate compete with any aggregates they encounter leading to the gradual formation of a single aggregate. Simultaneously, a positive feedback mechanism drives the formation of a single MT aster - a single loose aggregate leads to focused MT nucleation and hence a tighter aggregate which stabilizes MT minus ends more effectively leading to aster formation. We translate the model assumptions based on experimental measurements into mathematical equations. The model analysis and computer simulations successfully reproduce the observed pathways of pigment aggregation and microtubule aster self-organization. We test the model predictions by observing the self-organization in fragments of various sizes and in bi-lobed fragments. The model provides stringent constraints on rates and concentrations describing microtubule and motor dynamics, and sheds light on the role of polymer dynamics and polymer-motor interactions in cytoskeletal organization.