Collaborative Research: Understanding Thermal-Noise-Based Mechanisms for Intracellular Motion, with Application to Engineered Systems

设计大量小颗粒（从微米大小到大分子）同时定向运动的新能力，将对医学、电子和生物材料的各个领域产生巨大影响。这种定向运动是正常细胞内功能的组成部分，其中运动蛋白将环境电化学电位和随机热搅拌转化为运动，并充当微小的货物搬运工。该项目将学习并建立在这些生物机制的基础上，以创建一个框架，促进大量微尺度和亚微尺度粒子的强大和有效的集体运动。为这个项目创造的创新仪器将探测作用在运动蛋白上的力。微尺度粒子的工程运动的实现将为电子和生物医学带来新材料。新的分析技术将在相关研究中得到应用，例如细胞运输功能障碍在疾病中的作用。该项目将采用以下两种基于布朗棘轮的方法，以获得在微观尺度上运输货物的强大而有效的机制：(i)塑造光场以准确实现所需的势能景观，使布朗棘轮机制能够在噪声中实现有用的工作；（ii）了解运动蛋白和微管等生物成分如何使用布朗棘轮来实现运动，并使用这些结构来移动工程货物。光学棘轮机构将采用现代控制技术来实现。为了研究生物蛋白运动，将使用现代控制和系统工具来获得比目前最先进的探针至少快一个数量级的探针。使用光学陷阱研究运动蛋白的新模式将包括张力和力夹，这将有助于对分子运动的明确解释。为实现基于布朗棘轮的定向运动，将推导出创新的光力场开闭环控制律。

The emerging ability to engineer the simultaneous directed motion of large numbers of small particles, from micrometer size down to large molecules, will have tremendous impact in diverse areas of medicine, electronics and bio-materials. Such directed motion is an integral part of normal intracellular function, where motor proteins convert ambient electrochemical potentials and random thermal agitation into motion and act as tiny cargo haulers. This project will learn from and build upon these biological mechanisms, to create a framework for facilitating robust and efficient collective motion of large numbers of microscale and submicroscale particles. Innovative instrumentation created for this project will probe forces acting on motor proteins. Realization of engineered motion of microscale particles will lead to new materials for electronics and biomedicine. The new analytical techniques will find use in related studies, such as on the role of cellular transport malfunctions in disease. This project will employ the following two Brownian ratchet based approaches to obtain robust and efficient mechanisms for transporting cargo at the microscale: (i) shape optical fields to accurately realize desired potential energy landscapes that enable Brownian ratchet mechanisms where noise enables useful work, and (ii) understand how biological components such as motor proteins and microtubules employ Brownian ractchets to achieve motion, and use these constructs for moving engineered cargo. Optical ratchet mechanisms will be realized using modern control techniques. For studying bio-protein motion, modern controls and systems tools will be used to obtain probes at least an order of magnitude faster than the present state-of-the-art. New modes of investigating motor proteins using optical traps will include tension and force clamps, which will facilitate unambiguous interpretation of molecular motion. Innovative open- and closed-loop control laws for optical force fields will be derived to realize Brownian ratchet based directed motion.