Complex Bio-Nano-Dynamics of Motor Proteins in Dynamically Controlled Fluids

动态控制流体中运动蛋白的复杂生物纳米动力学

• 批准号: 1161874
• 负责人: Bogdan Epureanu
• 金额: $ 32万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1161874&HistoricalAwards=false
• 关键词: Complex; Bio; Nano; Dynamics; Motor

The recent breathtaking advances in modern engineering and bioscience research have enabled the identification of properties and roles of biomolecules that power cellular processes. The hallmark of these nanoscale systems is their multi-scale organization. In neurodegenerative diseases for example, axonal degeneration occurs because the neurotransmitters do not reach the synapse correctly. This is because binding of kinesins on microtubules is hindered. Hence, interrogating the properties of the nanotransport done by kinesins on microtubules is crucial for early/presymptomatic diagnosis of neurodegenerative diseases. Such early diagnosis will be enabled the novel models developed in this work. The goal of this work is to create an innovative approach to model and to actively interrogate the complex bio-nanotransport of groups of kinesins interacting with microtubules in controlled fluids. Specific aims are: (a) novel models: develop new models which bridge the gap between nano/pico length/time scales and macroscales through combined atomistic/continuum modeling and experiments, and (b) novel detection: create novel methods to interrogate kinesin-MT systems about their properties by monitoring the nanotransport done by these systems in controlled fluids. Uniquely combined theoretical and experimental methods from atomistic simulations, nonlinear dynamics and bioengineering are used. This effort will answer important scientific questions, and will impact applications spanning from cell science to biomolecular nanotechnology and engineered biodevices. For example, understanding how to model motor proteins in controlled fluids and how to identify properties of nanotransport in vivo is a key element in the next generation of drug technology and delivery, and can profoundly impact medicine. This work contributes to such understanding by using nonlinear dynamic approaches for solving very important questions in medicine and cell biology. If successful, this research can radically transform the way neurodegenerative diseases are diagnosed. Also, this work will provide fundamental understanding of bio-mechanochemical processes which affect the development of lab-on-a-chip bio-applications.

最近在现代工程和生物科学研究方面取得的惊人进展使人们能够识别为细胞过程提供动力的生物分子的特性和作用。这些纳米级系统的特点是它们的多尺度组织。例如，在神经退行性疾病中，轴突变性的发生是因为神经递质不能正确地到达突触。这是因为微管上驱动蛋白的结合受阻。因此，询问微管上驱动蛋白的纳米转运特性对于神经退行性疾病的早期/症状前诊断至关重要。这种早期诊断将使这项工作中开发的新模型成为可能。这项工作的目标是创造一种创新的方法来建模，并积极询问复杂的生物纳米运输组的驱动蛋白与微管在受控流体中相互作用。具体目标是：（a）新模式：开发新的模型，其通过组合的原子/连续体建模和实验来弥合纳米/皮科长度/时间尺度和宏观尺度之间的差距，以及（B）新颖的检测：创建新颖的方法来通过监测驱动蛋白-MT系统在受控流体中进行的纳米转运来询问这些系统的性质。从原子模拟，非线性动力学和生物工程的独特结合的理论和实验方法。这项工作将回答重要的科学问题，并将影响从细胞科学到生物分子纳米技术和工程生物设备的应用。例如，了解如何在受控流体中模拟马达蛋白以及如何识别体内纳米转运的特性是下一代药物技术和递送的关键因素，并且可以深刻影响医学。这项工作有助于通过使用非线性动力学方法解决医学和细胞生物学中非常重要的问题。如果成功，这项研究可以从根本上改变神经退行性疾病的诊断方式。此外，这项工作将提供影响芯片实验室生物应用发展的生物机械化学过程的基本理解。