Unraveling the pressure sensitivity of cytoskeletal microtubules

揭示细胞骨架微管的压力敏感性

• 批准号: 243249786
• 负责人: Professor Dr. Roland Winter
• 金额: --
• 依托单位: Lehrstuhl für Physikalische Chemie I
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243249786?language=en
• 关键词: Unraveling; pressure; sensitivity; cytoskeletal; microtubules

The central goal of this proposal is to use high hydrostatic pressure (HHP) to achieve an overall biophysical description of the conformational and energy landscape of important and pressure-sensitive non-covalent cytoskeletal polymers. In the first funding period we established a HHP-measuring platform based on spectroscopic, X-ray scattering and microscopic techniques that provided deep insights and detailed mechanistic descriptions of the pressure sensitivity of actin polymerization and bundling processes, also considering factors that can be encountered inside the cell (i.e., the effect of macromolecular crowding, the presence of osmolytes and accessory binding proteins). In the second funding period we will focus on the pressure perturbation of microtubule assembly and dynamics by studying its effect thermo-dynamically, kinetically and structurally with high spatial and temporal resolution. Combined with the results obtained from our pressure studies on the microfilaments, the new experiments will yield new insights into the mechanistic strategies for pressure resistance of cellular dynamics and movements found in living beings thriving under extreme environmental conditions. Such studies will also be valuable for biotechnological applications requiring an extended temperature-pressure process parameter range.

该提案的中心目标是使用高静水压力（HHP）来实现重要的和压力敏感的非共价细胞骨架聚合物的构象和能量景观的整体生物物理描述。在第一个资助期内，我们建立了一个基于光谱、X射线散射和显微镜技术的HHP测量平台，该平台提供了对肌动蛋白聚合和成束过程的压力敏感性的深刻见解和详细的机理描述，还考虑了细胞内可能遇到的因素（即，大分子拥挤效应、渗透剂和辅助结合蛋白的存在）。在第二个资助期内，我们将重点关注微管组装和动力学的压力扰动，通过研究其热动力学，动力学和结构上的影响，具有高的空间和时间分辨率。结合我们对微丝压力研究的结果，新的实验将对极端环境条件下生物中细胞动力学和运动的抗压机制策略产生新的见解。这些研究对于需要扩展温度-压力工艺参数范围的生物技术应用也将是有价值的。