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

最近在现代工程和生物科学研究方面取得的令人惊叹的进展使人们能够识别为细胞过程提供动力的生物分子的性质和作用。这些纳米级系统的标志是它们的多尺度组织。例如，在神经退行性疾病中，轴突退化是因为神经递质没有正确到达突触。这是因为运动蛋白与微管的结合受到了阻碍。因此，询问运动蛋白在微管上完成的纳米转运的特性对于神经退行性疾病的早期/症状前诊断至关重要。这项工作中开发的新模型将使这种早期诊断成为可能。这项工作的目标是创造一种创新的方法来模拟和积极询问受控流体中与微管相互作用的一组动蛋白的复杂生物纳米传输。具体目标是：(A)新模型：通过结合原子/连续介质建模和实验，开发新的模型，以弥合纳米/微微/时间尺度和宏观尺度之间的差距；(B)新的检测：通过监测Kinesin-MT系统在受控流体中的纳米传输，创造新的方法来询问这些系统的特性。采用了原子模拟、非线性动力学和生物工程等独特的理论和实验相结合的方法。这一努力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对马达蛋白质进行建模，以及如何识别体内纳米传输的特性，是下一代药物技术和给药的关键因素，并可以深刻影响医学。这项工作有助于通过使用非线性动力学方法来解决医学和细胞生物学中的非常重要的问题。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，这项工作将提供对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。

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.