Grants and Contracts Details
Description
Project Summary
Overview
The vision of this proposal is to overcome a key barrier to the development of magnetogenetics by elucidating the nanoscale energy conversion in magnetic nanoparticle heating. Magnetogenetics is a revolutionary biological technology that employs an alternating magnetic field (AMF) and magnetic nanoparticles to precisely control cell activities. In comparison to existing technologies like optogenetics, magnetogenetics offers a less invasive and wireless approach to controlling cells deep within the body, unlocking unprecedented opportunities for fundamental research and disease treatment. For instance, in the field of neuroscience, magnetogenetics holds great promise for probing brain functions and establishing brain-machine interfaces. However, the validity of magnetogenetics has been a subject of prolonged debate, primarily centered around the nanoscale energy conversion phenomena. Magnetic nanoparticle heating plays a central role in magnetogenetics by generating the necessary heat to activate thermally sensitive molecules responsible for regulating cellular functions. Therefore, this research aims to develop novel modeling and experimental methods to analyze magnetic nanoparticle heating at the nanoscale, providing a robust theoretical foundation for this revolutionary technology.
Magnetic nanoparticle heating has been extensively explored for thermal therapy, but its role in magnetogenetics remains elusive. These debates stem from the complex interplay of physical and chemical processes within the noisy biological environment that magnetogenetics operates in. Additionally, there is a lack of theoretical and experimental tools capable of analyzing nanoscale events at the individual nanoparticle level with a temporal resolution comparable to the frequency of the AMF (100 kHz to 1 MHz). Consequently, the current understanding of magnetogenetics relies on extrapolating macroscopic properties to the nanoscale, which challenges the classical Fourier heat conduction theory. To address these challenges, we propose to integrate novel modeling and experimental methods for comprehensive analysis of magnetic nanoparticle heating. Our hypothesis is that magnetic nanoparticle heating activates temperature-sensitive molecules through transient high heating at the nanoscale in a nonequilibrium manner. This proposed research will revolve around three main objectives: firstly, we will develop the first theoretical model capable of simulating the instantaneous states of individual magnetic iron oxide nanoparticles (MIONs) in an AMF; secondly, we will conduct in silico and in vitro analysis of transient heat generation and the production of reactive oxygen species (ROS) by both synthetic and biogenic MIONs; finally, we will employ well-characterized MIONs and molecular temperature probes to investigate the role of heat and ROS in the mechanisms underlying magnetogenetics.
Intellectual Merit
The project holds substantial intellectual merit due to its innovative theoretical model capable of analyzing both the transient behaviors of MIONs and their bulk heating properties. This aspect effectively bridges a current knowledge gap in the field of magnetic nanoparticle heating. Additionally, the project''s significance lies in the development of new experimental tools, including a library of MIONs with distinct magnetic and chemical properties and a highly sensitive and high throughput assay for investigating nanoscale heat transfer. Ultimately, the successful execution of the project will establish a robust theoretical foundation for magnetogenetics and provide essential guiding principles for the rational design of AMF-responsive molecular switches for next-generation biomedical technologies.
Broader Impacts
This project aims to have far-reaching impacts on society through the development of a revolutionary technology. With its paradigm-shifting effects on fundamental research and healthcare, including neuroscience, cancer therapy, and organ preservation, this endeavor holds the promise of transforming these fields in unprecedented ways. Furthermore, it is committed to empowering the next generation of researchers by providing students with research experience on state-of-the-art nanotechnology and molecular biology through the integration of research, teaching, and training. Efforts will be made to increase the participation of students from underrepresented and low socioeconomic groups and woman engineers by utilizing established NIH and NSF training programs at the University of Kentucky.
Status | Active |
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Effective start/end date | 7/1/24 → 6/30/27 |
Funding
- National Science Foundation: $355,994.00
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