EAGER: Towards a Homeostatic Nanobio-Hybrid Mechanical System

自然界平衡降解与自我修复的能力使持久的机械活性结构成为可能。例如，负责心肌收缩的分子马达每隔几天就会更换一次，使肌肉能够泵血一百年。在当今的工程系统中，运动部件由于机械磨损和疲劳而老化，并且必须在系统离线时更换。这个早期概念的探索性研究资助（EAGER）项目的长期目标是创建在分子水平上自我更新的工程系统。该奖项支持将修复机制添加到纳米级运输系统的探索性研究。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能够保持自身功能状态的长寿命系统。如果机器和结构的使用寿命能够延长，并且能够避免服务中断，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体内生物结构的理解。该项目将扩大代表性不足的群体对工程的参与。推广活动将激励新一代高中生追求工程教育。生物分子马达使得能够构建具有生物传感、生物计算和纳米制造应用的主动纳米级运输系统，其中运载货物或功能化微管由表面粘附的驱动蛋白马达蛋白推动。过去的工作已经量化了微管的降解机制，由于表面粘附的驱动蛋白马达推动它前进的行动。该项目的目标是采取下一步行动，积极应对特定的退化机制。收缩和断裂的主要微管降解机制可以通过微管片段的聚合和融合而被生长所抵消。在实施这些自我修复机制方面存在重大技术挑战，并且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。该项目的结果将是一个潜在的转型过渡到“活”的工程系统，自我修复，即使用积极的，耗能的过程，以保持其功能状态在分子尺度上。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.