Biophysical Properties of Tubulin and Microtubules and Their Nano-Biotechnology Potential

微管蛋白和微管的生物物理特性及其纳米生物技术潜力

• 批准号: RGPIN-2018-03837
• 负责人: Tuszynski, Jacek
• 金额: $ 2.99万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712389
• 关键词: Biophysical; Properties; Tubulin; Microtubules; Their

This project is focused on the biophysical properties of one of the key proteins in plant and animal cells: tubulin and its polymerized form, microtubules. (Polymers are molecular structures that are assembled out of repeating subunits.) Hundreds of tubulin genes from various species (including human) have been sequenced, which provides an enormous amount of untapped information about evolutionary changes in the structure and the biophysical/biochemical properties of this protein. We intend to use this information in our study. We will analyze all available tubulin sequences and construct 3D models of the protein based on the known templates for tubulin found in the Protein Data Bank. We will also investigate several biophysical properties of microtubules such as electrostatic charges and their spatial distribution. The interactions of the key drugs known to bind to tubulin will be investigated for the specificity of tubulin variants. This will enable us to create a map of interactions that can be affected by variations in the sequences of tubulin, which are known to occur in different cell types. Building off our previous work we will determine how specific amino acid changes between variants of tubulin affect the binding affinity between neighbouring tubulin molecules in the microtubule structure. This will inform us about both the static and dynamic mechanical properties of microtubules constructed from variants of tubulin. These results will fill a gap in the existing knowledge about the structure-to-function relationship of tubulin. In addition, we plan to continue our investigations of the electric conduction properties of microtubules, in collaboration with the Shankar group at the University of Alberta, to conclusively determine single microtubule conductance, capacitance, and possibly inductance (these are electrical properties), due to ionic current flows around microtubules. We intend to extend this nano-scale experimentation and couple it with computer modeling to study individual microtubules under various conditions of pH, ionic concentrations, temperature variations, and the presence of microtubule-associated proteins. Here, we plan to quantify these effects and to include AC conduction measurements in the range between 1 kHz and 1 MHz. This will enable the construction and characterization of complex architectures intended as micro-circuitry built from proteins and protein polymers. The ultimate objective of this aim is to provide a framework for creating nano-bio-electronic elements and combinations, for application as biodegradable and evolvable computing devices in the future. Our final interest in this project is to simulate the response of tubulin dimers to electromagnetic frequencies in several ranges (kHz, MHz, GHz and THz), in order to determine the sensitivity of tubulin structure to these fields, both for basic and applied biophysics considerations.

该项目的重点是植物和动物细胞中关键蛋白质之一的生物物理特性：微管蛋白及其聚合形式，微管。（聚合物是由重复亚基组装而成的分子结构。） 来自不同物种（包括人类）的数百个微管蛋白基因已被测序，这提供了关于该蛋白质的结构和生物物理/生物化学性质的进化变化的大量未开发的信息。我们打算在研究中使用这些信息。我们将分析所有可用的微管蛋白序列，并根据蛋白质数据库中发现的微管蛋白的已知模板构建蛋白质的3D模型。我们也将研究微管的一些生物物理性质，如静电荷及其空间分布。将研究已知与微管蛋白结合的关键药物的相互作用，以确定微管蛋白变体的特异性。这将使我们能够创建一个相互作用的地图，可以受到微管蛋白序列变化的影响，这是已知的发生在不同的细胞类型。基于我们以前的工作，我们将确定微管蛋白变体之间的特定氨基酸变化如何影响微管结构中相邻微管蛋白分子之间的结合亲和力。这将告诉我们从微管蛋白的变体构建的微管的静态和动态力学性质。这些结果将填补现有的知识空白的结构与功能的关系微管蛋白。 此外，我们计划继续我们的微管的导电性能的调查，在阿尔伯塔大学的Shankar组合作，最终确定单个微管电导，电容，并可能电感（这些都是电性能），由于离子电流在微管周围流动。我们打算扩展这种纳米尺度的实验，并将其与计算机建模相结合，以研究在pH值，离子浓度，温度变化和微管相关蛋白存在的各种条件下的单个微管。在这里，我们计划量化这些影响，并包括在1 kHz和1 MHz之间的范围内的AC传导测量。这将使复杂架构的构建和表征成为可能，这些架构旨在作为由蛋白质和蛋白质聚合物构建的微电路。这个目标的最终目标是提供一个框架，创造纳米生物电子元件和组合，在未来的生物降解和可进化的计算设备的应用。 我们在这个项目中的最后兴趣是模拟微管蛋白二聚体在几个范围内（kHz，MHz，GHz和THz）的电磁频率的响应，以确定微管蛋白结构对这些领域的敏感性，无论是基本的还是应用的生物物理学考虑。