Molecular-scale Breaking due to Repeated Loading in Molecular Shuttles

分子穿梭重复加载导致分子尺度断裂

• 批准号: 1662329
• 负责人: Henry Hess
• 金额: $ 45.24万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1662329&HistoricalAwards=false
• 关键词: Molecular; scale; Breaking; due; Repeated

The rate at which machines degrade with use has a large impact on their value. For example, modern cars last significantly longer than cars built only thirty years ago due to diligent research into failure modes and subsequent design improvements. Nanotechnology has progressed so that we can successfully build nanomachines such as 'molecular shuttles': nanoscale transport systems powered by biomolecular motors capable of delivering molecular cargo. The goal of this project is to advance our understanding of the degradation mechanisms limiting the lifetime of these molecular shuttles. The PIs research showed that 'mileage' matters - for every thousandth of an inch of distance moved, the molecular shuttle shrank a few nanometers in length. In this research project, the PIs will investigate if the course matters as well, and let the molecular shuttles travel through increasingly curvy microfabricated tracks which puts mechanical stress on their structure and should cause them to break at increasing frequencies. These experiments will improve understanding of degradation mechanisms for nanomachines in general, enable improvement of the design of our 'molecular shuttles', and may even provide insights into how biological nanomachines degrade and age. The project will integrate undergraduate researchers and high school students, and the new insights will be integrated into a new nanobiotechnology course. Outreach activities include lab activities and lectures as part of the 'Introduction to Nanotechnology' summer course for underrepresented high school students,The project is guided by two hypotheses. Firstly, it is our hypothesis that breaking events will occur stochastically at average rates determined by mechanochemical principles. Secondly, it is our hypothesis that the overall degradation of molecular shuttles in engineered environments can be understood as a combination of breaking and shortening of the microtubule component. To test these hypotheses, we will observe microtubules moved by kinesin motors (our basic 'molecular shuttle') through microfabricated guiding structures which exert a defined amount of constant and cyclic strain on the microtubule. The outcome of the project will be a potentially transformational broadening of our perspective from the physics-inspired force spectroscopy of intermolecular bonds (measuring e.g. rupture forces) to an engineering-inspired view of an accumulation of damage as result of mechanical stress in nanomachines, which may ultimately result in fracture. More immediately, the results of the project will help the community to overcome the limited lifetime roadblock in the design of nanodevices based on biomolecular motors.

机器随着使用而退化的速度对它们的价值有很大的影响。例如，现代汽车的使用寿命明显长于三十年前制造的汽车，这是由于对故障模式的勤奋研究和随后的设计改进。纳米技术的进步使我们能够成功地建造纳米机器，如“分子梭”：由生物分子发动机提供动力的纳米级运输系统，能够运送分子货物。该项目的目标是促进我们对限制这些分子穿梭机寿命的降解机制的理解。PI的研究表明，“里程”很重要--每移动千分之一英寸的距离，分子穿梭机的长度就会缩小几纳米。在这个研究项目中，PI将调查课程是否也很重要，并让分子穿梭机通过越来越弯曲的微加工轨道，这会对它们的结构施加机械应力，并导致它们以越来越高的频率断裂。这些实验将提高对纳米机器一般降解机制的理解，使我们的“分子梭”的设计得到改进，甚至可能提供对生物纳米机器如何降解和老化的见解。该项目将整合本科研究人员和高中学生，新的见解将被整合到一个新的纳米生物技术课程。外展活动包括实验室活动和讲座，作为代表性不足的高中生的“纳米技术入门”暑期课程的一部分，该项目由两个假设指导。首先，它是我们的假设，破碎事件将随机发生的平均速率所确定的机械化学原理。其次，我们的假设是，在工程环境中分子穿梭的整体降解可以理解为微管组分的断裂和缩短的组合。为了验证这些假设，我们将通过微制造的引导结构观察由驱动蛋白马达（我们的基本“分子梭”）移动的微管，该引导结构对微管施加确定量的恒定和循环应变。该项目的结果将是我们的视角从分子间键的物理学启发的力谱（测量例如断裂力）到纳米机器中机械应力导致的损伤积累的工程启发的观点的潜在转型拓宽，这可能最终导致断裂。更直接的是，该项目的结果将帮助社区克服基于生物分子马达的纳米器件设计中的有限寿命障碍。

项目成果

Designing a Hybrid Engineering Course combining Case-Based and Lecture-Based Teaching

案例教学与讲座教学相结合的混合工程课程设计

• DOI: 10.1109/embc.2018.8512572
• 发表时间: 2018
• 期刊: 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC
• 作者: Kazeruni, Neda M.;Laboy, Andre;Hess, Henry
• 通讯作者: Hess, Henry

Microtubule Detachment in Gliding Motility Assays Limits the Performance of Kinesin-Driven Molecular Shuttles

• DOI: 10.1021/acs.langmuir.0c01002
• 发表时间: 2020-07-14
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Kazeruni, Neda M. Bassir;Rodriguez, Juan B., III;Hess, Henry
• 通讯作者: Hess, Henry

Kinesin-propelled label-free microtubules imaged with interference reflection microscopy

用干涉反射显微镜成像驱动蛋白驱动的无标记微管

• DOI: 10.1088/1367-2630/abb47b
• 发表时间: 2020
• 期刊: New Journal of Physics
• 影响因子: 3.3
• 作者: Saper, Gadiel;Hess, Henry
• 通讯作者: Hess, Henry

Assembling Molecular Shuttles Powered by Reversibly Attached Kinesins

组装由可逆连接的驱动蛋白驱动的分子梭

• DOI: 10.3791/59068
• 发表时间: 2019
• 期刊: Journal of Visualized Experiments
• 作者: Bassir Kazeruni, Neda M.;Tsitkov, Stanislav;Hess, Henry
• 通讯作者: Hess, Henry