Invited Talk

Size, Force, and Entropy at the Cellular Interface

Department of Otolaryngology, University of California, San Francisco (UCSF), USA

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Juxtacrine signaling mediates communications via physical contact between neighboring cells, orchestrating development and physiology of multicellular organisms. The signal-exchange interfaces create unique microenvironments that biophysically constrain the arrangement and activity of protein, lipid, and glycan components, finally mediating the spatial organization and biochemical activity of signaling molecules, serving as the basis for wide-range of cellular functions. 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 mechanogenetics1-4 (i.e., targeted control of genetically encoded mechanosignaling), magnetically amplified protein-protein signals (MagAPPs)5, and single particle tracking6, 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 sequences6. From these observations, we disentangled a long-standing mystery of how dynamic compartmentalization and colocalization of Notch creates enzymatically distinct environments and hence facilitates sequential proteolysis of Notch and signaling6.