Cooperative Nonlinear Dynamics of Motor Proteins

在过去的三十年里，现代工程和生物科学研究都见证了实验和理论的进步，这些进步导致了纳米到微米尺度工程和生物分子研究的出现，成为基础探索和应用的主要焦点。本研究关注生物分子马达的性质和相互作用，生物分子马达是无处不在的纳米级蛋白质机器，主要负责真核细胞内的纳米至微米级运输过程。这些系统的特点是它们复杂的动力学和组织，这被广泛认为是理解，操纵和最终控制这些系统用于（生物）技术用途的关键。本论文的主要目标是研究和探索多个分子马达协同工作的非线性动力学机制，这一工作将回答几个关键的科学问题，并将影响大量的应用。了解马达蛋白如何发挥作用并合作运输货物是药物输送和设计等应用中的关键工程要素，并具有影响医学的强大潜力（例如帕金森病和癌症等一系列疾病的临床范式和治疗）。这种理解可以通过诸如本文提出的方法来获得，其中定量的非线性动力学方法用于解决细胞生物学中的这个重要问题。此外，拟议的工作将提供生物机械化学过程的基本理解和分析工具。该提案包括强有力的综合教育部分和外联活动。

During the last three decades both modern engineering and bioscience research have witnessed experimental and theoretical advances which have led to the emergence of nano- to microscale engineering and biomolecular research as major focus for fundamental exploration and applications. This research is concerned with the properties and interactions of biomolecular motors, ubiquitous nanoscale protein machines that are principally responsible for nano- to microscale transport processes insides eukaryotic cells. The hallmark of these systems is their complex dynamics and organization which are widely believed to be crucial for understanding, manipulating, and finally controlling these systems for (bio-) technological use. The main goal of the work is to characterize and exploit the nonlinear dynamic mechanisms which govern the cooperative behavior of multiple molecular motors carrying a common cargo.The proposed work will answer several crucial scientific questions, and will impact a large number of applications. Understanding how motor proteins function and cooperate to transport cargoes is a key engineering element in applications such as drug delivery and design, and has a strong potential to impact medicine (e.g.clinical paradigms and treatments of an array of diseases such as Parkinson's and cancer). Such understanding can be obtained by an approach such as proposed herein, where quantitative, nonlinear dynamics approaches are used to solve this important problem in cell biology. Also, the proposed work will provide fundamental understanding and analysis tools for bio-mechano-chemical processes. The proposal includes strong integrated educational components and outreach activities.