Murphy, Daniel B
Robinson, Jacob T
Master of Science
Noninvasive control of the electrical activity in specific cells in the brain would transform fundamental neuroscience research and the development of therapeutic technologies. Current neural stimulation methods such as electrical or optogenetic stimulation achieve high levels of specificity, but are invasive. Magnetic stimulation is a potentially noninvasive stimulation modality because mammalian tissue is nearly transparent to magnetic fields. In this thesis we investigate a new neural modulation method based on magnetic fields that can potentially achieve similar levels of specificity with much lower invasiveness. Our method will use externally applied, uniform magnetic fields that induce dipole-dipole forces between superparamagnetic iron oxide nanoparticles bound to Piezo1, a mechanically sensitive ion channel. Based on our calculations and early preliminary results, these mechanical forces will be sufficient to open Piezo1, leading to cationic currents, that will alter cell activity. Expression of mutant Piezo1 protein can be targeted to genetically specific populations of cells by means of cell-type specific promoters in transgenic animals. This method is expected to achieve accurate control of genetically specific populations of cells, thereby enabling better research to answer fundamental biological questions and develop novel medical therapies.
magneto-mechanical; neuromodulation; mechanotransduction; Piezo1; magnetogenetics