Many biological processes depend on proper functioning and maintenance of cellular electric fields. As such, measurement of electrical activities within living cells is essential in understanding the electrophysiology of a cell and associated disease states. To date, most of what is known about cellular electrical activities are derived from measurements made across cell membrane, and not in the internal bulk of the cell, due to technical limitations. Methods such as patch and voltage clamps and fluorescent resonance energy transfer involve direct interactions with, or are constrained to membrane components. While some voltage-sensitive dyes may provide a more flexible platform, they are not optimal for measuring electrical changes throughout the cell.
Researchers at the University of Michigan have developed a wireless nano-optical voltmeter to effectively measure electric fields of the entire cell volume. This invention is based on PEBBLE (Probes Encapsulated By Biologically Localized Embedding) system, where each voltmeter is a nanoparticle encapsulating a voltage-sensitive dye. The voltmeters are approximately 30 nanometers in size, or about 1000 times smaller than existing voltmeters, and are coated to facilitate their entrance into the cells and minimize cytotoxicity. Unlike the voltage sensitive dye alone, PEBBLEs solution provides extra stability in addition to calibration stability. Furthermore, PEBBLEs may not be sequestered into cell membranes, as do dyes, which enable use in extracellular space as well as in the cytosol, previously not possible. Selective targeting of the voltmeters to specific locations inside the cells can be achieved via modification in their coatings. Using this novel system, electric field fluctuation throughout the entire cell can be measured, enabling 3-dimensional mapping of live cells.
Applications and Advantages
- measurement of electric fields for non-biological-nl-and biological samples, including in the cytosol-nl-and in the extracellular space
- increased overall calibration stability-nl-compared to voltage sensitive dyes alone
- can be targeted to specific cell types
- not sequestered into cell membrane,-nl-enabling electric field measurements-nl-within the cytosol
- 3-dimensional imaging of cell electric fields