Notch signaling is a highly conserved cell-to-cell communication mechanism, which plays a central role in defining individual cells'behaviors and fates during development. Despite rapidly increasing knowledge of these signaling events, little is known about how spatiotemporal dynamics of receptor signaling across the cell influence signal exchange. To address this challenge, we propose an advanced nanosystem that mimics, enabling simultaneous real-time monitoring and in situ regulation of Notch signaling in a particular cell at any desired location and time with subcellular resolution. Using this new nanotechnology, we first determine force-induced structural features of Notch receptors. We also explore Notch signaling in neural stem cells to determine how the spatiotemporal distribution of Notch signaling across a cell population influences the final fate of individual cels during development. Binary cell communication via Notch.
The proposed new single molecule probes with extreme brightness, high-resolution, photo stability, and magnetic tweezing capability will provide not only specific and sensitive diagnostic tools but also the ability to control stem cell differentiaton with single cell resolution, which has implications for stem cell therapy. Moreover, Notch signaling is an important protein involved in the development of many diseases such as cancer, multiple sclerosis, lymphoma, and other diseases, and thus the understanding of Notch dynamics will be beneficial for diagnostic and therapeutic purposes.
|Seo, Daeha; Southard, Kaden M; Kim, Ji-Wook et al. (2016) A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time. Cell 165:1507-18|