Understanding Fundamental Mechanisms that Underlie Nano-Neuro Interactions

Washington University, Saint Louis MO

Investigators

Abstract

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.