Interrogating the Fundamental Mechanisms of Mechanical Neuromodulation at the Nanoscale

Brain disorders affect millions of people worldwide, yet effective treatment options remain limited. Ultrasound neuromodulation is a promising technique that uses sound waves to gently influence brain activity without surgery. However, scientists do not fully understand how ultrasound affects individual brain cells, which limits its safe and effective use in medicine. This project will uncover how mechanical forces created by ultrasound interact with neurons at length scales smaller than a single cell. The research will explore whether, where, and how the mechanical energy is delivered to a neuron and how that neuron responds. The results of the project will guide the development of new brain therapies. The project will also include educational activities designed to foster curiosity in bio-inspired photonics and neuroscience. Together, the outcomes of this project will inform the development of future healthcare biotechnology and spur interest in bioengineering in the next generation of scientists and engineers. The project will develop a new laboratory tool that will allow scientists to apply highly controlled mechanical forces to specific regions of individual neurons and monitor their response in real-time. This tool will use light to generate forces, enabling precise control over where the force is applied and how it changes over time. These light-driven forces are designed to mimic key features of ultrasound stimulation, including force strength, timing, frequency, and duration. Unlike existing methods, which often rely on blunt mechanical probes or large ultrasound devices, this new approach will allow each parameter to be adjusted independently. It will combine a gold nanostructure that converts light into localized sound waves with a highly sensitive microscope capable of measuring very small forces. By carefully measuring how neurons respond to well-defined mechanical signals, the research will identify which force characteristics are most important for activating or suppressing neuronal activity. The knowledge gained from this research will help clarify the physical principles behind ultrasound neuromodulation and guide the design of future brain stimulation technologies. 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. NSF Award ID: 2528704 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Yang Zhao | Institution: University of Illinois at Urbana-Champaign, URBANA, IL | Award Amount: $395,787 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2528704 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2528704.html