Polyelectrolyte Nature of Cytoskeleton Filaments

肌动蛋白细丝(F-Actin)和微管(MTS)是由以下物质形成的高电荷棒状聚电解质 G-肌动蛋白和微管蛋白亚基的聚合。这些细胞骨架细丝是必不可少的 用于真核细胞的定向生长、形状、分裂等重要生物学活动 流程。在病理条件下，G-肌动蛋白/微管蛋白基因的突变经常是明显的。肌动蛋白 突变可能导致扩张型或肥厚型心肌病、先天性骨骼肌病和 耳聋。而微管蛋白突变与胎儿皮质发育畸形有关。 当细胞内生物环境发生变化时，即使是正常的G-肌动蛋白和微管蛋白 基因与F-肌动蛋白/MTS的功能障碍和畸形有关，如调控失调 组装、误导蛋白质结合、聚合稳定性异常和电信号缺陷 变速箱。细胞骨架丝传递电信号和克服静电的基础 形成束和网络的相互作用似乎主要由聚电解质的性质所主导 这些细丝而不是它们的三级结构。然而，潜在的生物物理原理和 支持F-肌动蛋白和MTS聚电解质性质的分子机制及其性质 由于缺乏适当的方法，人们对此仍然知之甚少。在本研究项目中， 提出了一种创新的细胞骨架细丝平衡方法，以达到精确和高效的平衡 具有实验技术的计算工具，使得第一次有可能 全面、高效地刻画电信号在电信号传播过程中的捆绑形成 许多细胞内环境和细丝分子结构，通常存在于正常 以及病态的情况。据推测，分子和/或细胞的改变，通常在 年龄和遗传引起的病理状态，打破平衡和相互竞争 控制细胞骨架捆绑和传导特性的分子机制 正常情况下的细丝。这项研究提案的总体目标是确定 细胞内环境的过度变化和细丝电荷的变化 细胞骨架细丝聚电解质特性的异构体和突变。这样做的结果是 该提案有望提供前所未有的关于为什么以及如何年龄和年龄的分子理解 遗传条件会导致细胞骨架细丝功能障碍和畸形。这 了解可能会促进各种疾病的预防和/或治疗。它也可能会打开 神经科学中尚未探索的前沿领域。它可能会阐明细胞骨架细丝和轴突 膜能够传递不同种类的信息，以及电的作用可能是什么 神经元类缆索理论中的信号沿细丝传播。

Actin filaments (F-actin) and microtubules (MTs) are highly charged rod-like polyelectrolytes formed by polymerization of G-actin and tubulin subunits, respectively. These cytoskeleton filaments are essential for directional growth, shape, division and other important biological activities in eukaryotic cellular processes. Mutations in G-actin / tubulin genes are often evident in pathological conditions. Actin mutations may cause dilated or hypertrophic cardiomyopathies, congenital skeletal myopathies and deafness. Whereas tubulin mutations are associated with fetal malformations of cortical development. When subjected to intracellular biological environment alterations, even normal G-actin and tubulin genes are associated with dysfunctions and malformations in F-actins / Mts such as dysregulated assembly, misleading protein binding, abnormal polymerization stability, and defective electric signal transmission. The basis for cytoskeleton filaments to transmit electric signals and overcome electrostatic interactions to form bundles and networks appears primarily dominated by the polyelectrolyte nature of these filaments rather than their tertiary structures. However, the underlying biophysical principles and molecular mechanisms that support the polyelectrolyte nature of F-actin and MTs, and their properties are still poorly understood due to the lack of appropriate methodologies. In this research project an innovative approach for cytoskeleton filaments is proposed to balance accurate and efficient computational tools with experimental techniques, making it possible for the first time, to comprehensively and efficiently characterize bundling formation and electric signal propagation under the numerous intracellular environments and filament molecular structures that are usually present in normal and pathological conditions. It is hypothesized that molecular and/or cellular alterations, often evident in pathological conditions caused by age and inheritance, break down equilibrium and competition between the molecular mechanisms that dominate the bundling and conducting properties of cytoskeleton filaments in normal conditions. The overall goal of this research proposal is to determine the impact of excessive alterations in the intracellular environment and variations in the filament charge produced by isoforms and mutations on the polyelectrolyte properties of cytoskeleton filaments. The outcomes of this proposal is expected to provide an unprecedented molecular understanding on why and how age and inheritance conditions induce dysfunctions and malformation in cytoskeleton filaments. This understanding may advance the prevention and/or treatment of a variety of diseases. It may also open unexplored frontiers in neuroscience. It might elucidate whether cytoskeleton filaments and axon membranes are able to transmit different kind of information and what might be the role of electrical signal propagation along filaments in neuronal cable-like theories.