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经历了实验和理论的进步，导致了纳米到微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。这项研究涉及生物分子马达的性质和相互作用，生物分子马达是普遍存在的纳米级蛋白质机器，主要负责真核细胞内从纳米到微米的运输过程。这些系统的特点是其复杂的动力学和组织，人们普遍认为这对理解、操纵和最终控制这些系统用于(生物)技术用途至关重要。这项工作的主要目的是描述和开发控制多个分子马达承载共同货物的合作行为的非线性动力学机制。所提出的工作将回答几个关键的科学问题，并将影响到大量的应用。了解马达蛋白质如何发挥作用并协作运输货物是药物输送和设计等应用中的关键工程元素，并具有极大的潜力影响医学(例如，临床范例和一系列疾病的治疗，如帕金森氏症和癌症)。这样的理解可以通过如本文提出的方法获得，其中使用定量的、非线性动力学方法来解决细胞生物学中的这一重要问题。此外，拟议的工作将为生物机械化学过程提供基本的理解和分析工具。该提案包括强有力的综合教育内容和外联活动。

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.