Relating interactions between neurofilaments to the structure of axonal neurofilament distributions through polymer brush models
Relating interactions between neurofilaments to the structure of axonal neurofilament distributions through polymer brush models
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DOI：
10.1016/s0006-3495(02)75581-1
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发表时间：
2002-05-01
影响因子：
3.4
通讯作者：
Paulaitis, ME
中科院分区：
文献类型：
--
作者：
Kumar, S;Yin, XH;Paulaitis, ME
神经丝被认为是通过相互空间排斥其非结构的C-末端“侧臂”结构域而相互作用的，在轴突的分布中产生有序的神经丝，并赋予轴突机械强度。在这里，我们应用为聚合物刷子开发的理论来检查侧臂的刷子特性与轴突中的神经纤维组织之间的关系。我们首先测量了成年小鼠的核因子-核因子径向分布函数和占用概率分布。用信息论解释概率分布，我们证明了核函数的分布可以用平均力的单对势来表示。然后，为了探索模型参数与核子结构之间的关系，我们对核子核的截面分布进行了二维蒙特卡罗模拟。我们施加纯排斥相互作用势，其中侧臂表示为中性和聚电解质链。通过将非牛磺酸视为遥控聚合物刷子，我们还加入了交叉桥联作用。这两种排斥势都能够再现核素的截面密度和它们的对关联。我们发现，NF结构对链电荷介导的刷子厚度的变化很敏感，这与侧臂磷酸化调节丝间距的实验观察一致。有吸引力的交叉桥相互作用的存在只对中等程度的交叉桥的结构做出了适度的贡献，并导致了广泛交叉桥的核因子聚集。
Neurofilaments (NFs) have been proposed to interact with one another through mutual steric exclusion of their unstructured C-terminal "sidearm" domains, producing order in axonal NF distributions and conferring mechanical strength to the axon. Here we apply theory developed for polymer brushes to examine the relationship between the brush properties of the sidearms and NF organization in axons. We first measure NF-NF radial distribution functions and occupancy probability distributions for adult mice. Interpreting the probability distributions using information theory, we show that the NF distributions may be represented by a single pair potential of mean force. Then, to explore the relationship between model parameters and NF architecture, we conduct two-dimensional Monte Carlo simulations of NF cross-sectional distributions. We impose purely repulsive interaction potentials in which the sidearms are represented as neutral and polyelectrolyte chains. By treating the NFs as telechelic polymer brushes, we also incorporate cross-bridging interactions. Both repulsive potentials are capable of reproducing NF cross-sectional densities and their pair correlations. We find that NF structure is sensitive to changes in brush thickness mediated by chain charge, consistent with the experimental observation that sidearm phosphorylation regulates interfilament spacing. The presence of attractive cross-bridging interactions contributes only modestly to structure for moderate degrees of cross-bridging and leads to NF aggregation for extensive cross-bridging.