The capacity to both image and manipulate neural signaling, as epitomized by optogenetics, provides an unprecedented means of interrogating complex neural information processes. However, analogous manipulation of mechanotransduction ion channels has largely eluded control so far, despite their importance in neurosensory systems and a need to better understand their transduction mechanisms. To address this question, this application seeks to combine expertise in nanoscience, neuroscience, optical microscopy, and biophysical analysis. Specifically, we propose novel nanoprobing systems based on targeted and force- generating magnetoplasmonic nanoparticles (MPNs). We develop two innovative force microscopy tools including nanruler force microscopy and mechanogenetic nanomodules, enabling simultaneous imaging and delivery of mechanical stimuli to candidate force-transmission components with precise spatial, temporal, and quantitative resolutions. As an initial study, we will use these techniques to elucidate various hypothetic models of NOMPC-mediated force-transducing mechanisms. This study will accelerate our understanding of ion channel-based mechanotransduction processes and will provide nanotechnology platforms for the systematic investigation of operating principles of a wide range of mechanotransduction channels.
Loss of mechnosensation causes devastating problems including developmental defects, deafness, failures of risk mitigation and lack of coordinated body movement. The proposed research will greatly accelerate our understanding of the operating principles of mechnosensory systems and thus will be beneficial for designing artifical regeneration devices (e.g. cochlear transplantation).
| Kim, Ji-Wook; Jeong, Hee-Kyung; Southard, Kaden M et al. (2018) Magnetic Nanotweezers for Interrogating Biological Processes in Space and Time. Acc Chem Res 51:839-849 |
