Understanding Fundamental Mechanisms that Underlie Nano-Neuro Interactions

了解纳米神经相互作用的基本机制

• 批准号: 2331330
• 负责人: Srikanth Singamaneni
• 金额: $ 57.07万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2331330&HistoricalAwards=false
• 关键词: Understanding; Fundamental; Mechanisms; Underlie; Nano

Nanoparticles exhibit unique physical and chemical properties that are distinct from their bulk counterparts. Because of their tiny size and unique properties, nanoparticles have unique advantages as devices that can both sense and stimulate nerve cells (neurons). These unique properties can also be harnessed to develop new technologies that will help us in understanding how the brain works and in overcoming brain-related conditions such as Parkinson’s disease and epilepsy. Furthermore, nanomaterials are increasingly becoming common in everyday life. Although our body's defense system filters out many foreign substances, studies indicate that nanoparticles can still enter the central nervous system through various pathways. How these tiny particles interact with nerve cells is not well understood; this is a big obstacle to using them widely for recording and stimulating neurons and assessing their impact on the central nervous system. This project has two main goals: (1) to understand how and why certain nanoparticles naturally bind to neurons as they grow and mature; and (2) to determine how this binding affects the electrical properties and activity of neurons. Understanding these interactions could lead to better-designed nanoparticles for studying the brain and new, less invasive technologies for treating nerve-related disorders. This project is an important step in filling in our knowledge gaps and could have a big impact on society by helping us deal with serious nerve-related conditions. The PIs will continue their ongoing successful recruitment and training of graduate and undergraduate students from underrepresented groups in STEM fields and will develop a Nano-Neuro Summer School program aimed at middle school students, targeting those from groups underrepresented in STEM.Owing to their optimal dimensions and unique biophysicochemical properties, nanoparticles offer distinct advantages as neural sensors and stimulators. However, the lack of understanding of the basic mechanisms of nano-neuro interactions remains a critical bottleneck in the widespread use of functional nanostructures for recording and stimulating neurons. The primary objective of this project is two-fold: (i) to understand the mechanistic aspects of spontaneous and maturation-dependent binding of nanoparticles to neurons; and (ii) to determine the effect of nanoparticle binding on the electrophysiological properties and electrical activity of neurons. To achieve these goals, the PIs will: (1) investigate the effect of the magnitude of the nanoparticle charge on the maturation-dependent binding of nanoparticles to neurons; (2) explore the effect of the electrophysiological properties and electrical activity of neurons on nanoparticle binding; and (3) elucidate the effect of nanoparticle binding on the excitability of neurons. Successful completion of this project will advance scientific understanding of the nano-neuro interactions and can have a transformative impact on the design and synthesis of nanomaterials for neuroscience and minimally-invasive technologies for treating neuronal disorders. This project can have an important long-term societal benefit in overcoming the burden associated with these devastating neuropathological conditions. The PIs will continue their ongoing successful recruitment and training of graduate and undergraduate students from underrepresented groups in STEM fields and will develop a Nano-Neuro Summer School program aimed at middle school students, targeting those from groups underrepresented in STEM.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.

纳米颗粒表现出独特的物理和化学性质，是不同于他们的散装同行。由于其微小的尺寸和独特的性质，纳米粒子作为既可以感知又可以刺激神经细胞（神经元）的设备具有独特的优势。这些独特的特性也可以用来开发新技术，帮助我们了解大脑如何工作，并克服与大脑相关的疾病，如帕金森病和癫痫。此外，纳米材料在日常生活中越来越常见。虽然我们身体的防御系统可以过滤掉许多外来物质，但研究表明纳米颗粒仍然可以通过各种途径进入中枢神经系统。 这些微小的颗粒如何与神经细胞相互作用还不清楚;这是广泛使用它们记录和刺激神经元并评估它们对中枢神经系统影响的一大障碍。该项目有两个主要目标：（1）了解某些纳米粒子在生长和成熟时如何以及为什么与神经元自然结合;（2）确定这种结合如何影响神经元的电特性和活动。了解这些相互作用可能会导致更好地设计用于研究大脑的纳米颗粒，以及用于治疗神经相关疾病的新的侵入性较小的技术。这个项目是填补我们知识空白的重要一步，通过帮助我们处理严重的神经相关疾病，可能会对社会产生重大影响。 PI将继续成功招募和培训STEM领域代表性不足的研究生和本科生，并将开发针对中学生的Nano-Neuro暑期学校计划，目标群体是STEM领域代表性不足的群体。由于其最佳尺寸和独特的生物化学特性，纳米颗粒作为神经传感器和刺激器具有明显的优势。然而，缺乏对纳米神经元相互作用的基本机制的理解仍然是广泛使用功能性纳米结构记录和刺激神经元的关键瓶颈。该项目的主要目标是双重的：（i）了解纳米颗粒与神经元自发和成熟依赖性结合的机制方面;（ii）确定纳米颗粒结合对神经元电生理特性和电活动的影响。为了实现这些目标，PI将：（1）研究纳米颗粒电荷大小对纳米颗粒与神经元的成熟依赖性结合的影响;（2）探索神经元的电生理特性和电活动对纳米颗粒结合的影响;（3）阐明纳米颗粒结合对神经元兴奋性的影响。该项目的成功完成将促进对纳米神经元相互作用的科学理解，并可能对神经科学和治疗神经元疾病的微创技术的纳米材料的设计和合成产生变革性影响。该项目可以在克服与这些破坏性神经病理学状况相关的负担方面产生重要的长期社会效益。PI将继续成功招募和培训来自STEM领域代表性不足的群体的研究生和本科生，并将开发针对中学生的Nano-Neuro暑期学校计划，目标是来自STEM领域代表性不足的群体。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响力审查标准进行评估，被认为值得支持。