EAGER: Towards a Homeostatic Nanobio-Hybrid Mechanical System

大自然平衡退化和自我修复的能力使机械活性结构能够持久。例如，负责心肌收缩的分子马达每隔几天就会更换一次，从而使心肌能够泵血一百年。在当今的工程系统中，由于机械磨损和疲劳，运动部件会老化，并且在系统离线时必须更换。这个探索性研究（EAGER）项目的长期目标是创建能够在分子水平上自我更新的工程系统。该奖项支持在纳米级传输系统中添加修复机制的探索性研究。通过证明用特定的修复过程来对抗特定的降解过程的可行性，这项工作将表明可以构建一个维持自身功能状态的长寿命系统。如果可以延长机器和结构的使用寿命，避免服务中断，美国经济将受益匪浅。“活的”工程系统的设计也将促进我们对自己身体生物结构的理解。该项目将扩大代表性不足的群体在工程领域的参与。外展活动将激励新一代高中生追求工程教育。生物分子马达能够在生物传感、生物计算和纳米制造中构建活性纳米级运输系统，其中携带货物或功能化的微管是由表面粘附的马达蛋白驱动的。过去的工作已经量化了微管的降解机制，这是由于表面粘附的运动马达推动微管前进的作用。该项目的目标是采取下一步措施，积极对抗特定的降解机制。微管收缩和断裂的主要降解机制可以通过微管片段的聚合和融合来抵消。在实施这些自我修复机制方面存在重大的技术挑战，必须确定实现降解和自我修复平衡的稳定状态的可行性。具体来说，该项目将证明生长和融合可以精确量化和控制。该项目的结果将是向“活的”工程系统的潜在转型，这种系统可以自我修复，即使用主动的，耗能的过程来维持其在分子尺度上的功能状态。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Nature’s ability to balance degradation with self-repair enables long-lasting mechanically active structures. For example, the molecular motors responsible for the contraction of a heart muscle are replaced every few days, allowing the muscle to pump blood for a hundred years. In today’s engineered systems, moving parts age due to mechanical wear and fatigue and have to be replaced while the system is taken offline. The long-term goal of this EArly-concept Grant for Exploratory Research (EAGER) project is to create engineered systems which renew themselves at the molecular level. This award supports exploratory research into adding repair mechanisms to a nanoscale transport system. By demonstrating the feasibility of countering specific degradation processes with specific repair processes, the work will show that a long-lived system which maintains itself in a functional state could be constructed. The US economy will benefit significantly if the lifetime of machines and structures can be extended and interruptions in service can be avoided. The design of “living” engineered systems will also advance our understanding of the biological structures in our own bodies. The project will broaden the participation of underrepresented groups in engineering. Outreach activities will inspire a new generation of high school students to pursue an engineering education. Biological molecular motors enable the construction of active nanoscale transport systems with applications in biosensing, biocomputing and nanomanufacturing, where a cargo-carrying or functionalized microtubule is propelled by surface-adhere kinesin motor proteins. Past work has quantified the degradation mechanisms of microtubules due to the action of the surface-adhered kinesin motors propelling it forward. The goal of this project is to take the next step and to actively counteract specific degradation mechanisms. The primary microtubule degradation mechanisms of shrinking and breaking can be potentially counteracted by growth via polymerization and fusing of microtubule segments. Significant technical challenges in implementing these self-repair mechanisms exist and the feasibility of achieving a steady state where degradation and self-repair are balanced has to be determined. Specifically, the project will demonstrate that growth and fusing can be precisely quantified and controlled. The outcome of the project will be a potentially transformational transition towards “living” engineered systems, which self-repair, that is use active, energy-consuming processes to maintain their functional state at the molecular scale.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.