Actin filaments and microtubulus

肌动蛋白丝和微管

基本信息

批准号：
9207458
负责人：
Marcelo Marucho
金额：
$ 14.7万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-15 至 2018-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Recently it has been reported that actin filaments and microtubules are able to transmit electric signals and sustain ionic conductance. Since the velocity of electrical signals along these filaments is, depending on specific conditions, of same range as the propagation of neural impulses, the concurrent propagation of electrical signals along these filaments and electrochemical currents along the axonal membrane is possible in principle. This novel conduction mechanism observed in cells opens unexplored frontiers that will change the current understanding of neural activities and neuronal networks. Not surprisingly, the ionic conduction of these structures has been associated with processes as diverse as directional growth, cytotoxicity, plasticity, and migration. However, the underlying biophysical principles that support this behavior are poorly understood. Therefore, the objective of this proposed research is to generate substantial preliminary results to advance the molecular understanding of ionic conductance and electric signal transmission properties of microtubules and actin filaments. We believe that filaments and axon membranes may be able to transmit different kinds of information. Such capability may be affected by age and physiological conditions in different manner and therefore the corresponding propagation of electrical signal along filaments and neural axon membrane might be associated to different neural activity dysfunctions. Without question, investigating the biophysical principles underlying the electric and solvation properties of these cable-like filaments can bring an urgently needed progress in the molecular causes of many developmental and degenerative brain disorders. We may not validate our hypothesis and address this gap in knowledge using conventional models and approaches. Therefore one of the aims of this project consists in developing a computational tool to rationally investigate the electrophysiological mechanisms that affect conformational changes and conductance of electrical signals in both extra- and intracellular environments. We will perform a systematic characterization of these properties at a molecular level. This theoretical framework would also make great contributions to conventional areas of biochemistry where electrostatics underlies a major part of molecular properties. The proposed computational model will be then further extended to produce the mathematical engine to investigate signal transduction in proteins. The outcomes of this proposal will have a significant impact on the understanding and clinical applications of non-neuronal signal transduction and could open new therapeutic avenues to help the millions of patients currently affected by these disorders. In addition, the computational model (which will be publicly available) will enable the advancement of various technological and biomedical applications involving electrical conductance in proteins such as electrochemical biosensors, electric stimulation of tissue growth, and biomolecular processors.

描述（由申请人提供）：最近有报道称肌动蛋白丝和微管能够传输电信号并维持离子电导，因为根据具体条件，电信号沿着这些丝的速度与传播的范围相同。原则上，沿着这些细丝的电信号和沿着轴突膜的电化学电流的同时传播是可能的，这种在细胞中观察到的新颖的传导机制开辟了未探索的前沿。然而，这将改变目前对神经活动和神经网络的理解，毫不奇怪，这些结构的离子传导与定向生长、细胞毒性、可塑性和迁移等多种过程有关，这是支持这种行为的基本生物物理原理。因此，这项研究的目的是产生实质性的初步结果，以促进对微管和肌动蛋白丝的离子电导和电信号传输特性的分子理解。传输不同类型的信息。这种能力可能会以不同的方式受到年龄和生理条件的影响，因此电信号沿着细丝和神经轴突膜的相应传播可能与不同的神经活动功能障碍相关，毫无疑问，研究潜在的生物物理原理。这些电缆状细丝的电和溶剂化特性可以为许多发育性和退行性脑部疾病的分子原因带来迫切需要的进展，因此我们可能无法使用传统模型和方法来验证我们的假设并解决这一知识空白。该项目的目标包括开发一种计算工具来合理研究影响细胞外和细胞内环境中电信号构象变化和电导的电生理机制，我们将在分子水平上对这些特性进行系统表征。对静电学是分子特性主要部分的传统生物化学领域的贡献随后将进一步扩展以产生研究蛋白质信号转导的数学引擎。该提案的结果将对理解产生重大影响。及其临床应用此外，该计算模型（将公开）将促进涉及电导的各种技术和生物医学应用的发展。蛋白质，例如电化学生物传感器、组织生长的电刺激和生物分子处理器。