Spatiotemporal interrogation of molecular mechanobiology at the cell-cell signaling interface with nanotechnology tools
Young-wook Jun, Associate Professor (USCF/Yonsei)
Cell signaling is orchestrated by cooperative actions of multiple nanoscale biomolecular machines. These processes are highly dynamic in space and time, and aberrant spatiotemporal dynamics of cell signaling results in developmental defects and diseases. How cells choreograph these signaling sequences in space and time to regulate cell functions and fates is of a central question in biology. To interrogate spatiotemporal regulation of cell signaling, we have been developing various nanotechnology tools to image and manipulate cell signaling in space and time with single-cell and molecule resolution. In this talk, I will specifically focus on spatiotemporal dynamics of Notch, a key cell communication receptor, and its signaling consequences in cells. By integrating cutting-edge nanotechnology tools including mechanogenetics (i.e. targeted control of genetically encoded mechanosignaling), super-resolution microscopy, and single particle tracking, we mapped dynamic spatial distributions of Notch receptors during the cell surface activation. We discovered that Notch undergoes dynamic spatial changes immediately after its receptor activation, choreographing downstream cell signaling sequences. From these observations, we disentangled a long-standing mystery of how dynamic phase separation and colocalization of Notch creates enzymatically distinct environments and hence facilitates sequential proteolysis of Notch and signaling.