"Interrogation of spatial, temporal, and mechanical responses
of cell signaling with single-cell perturbation nanomodules"
Spatial segregation, clustering, scaffolding, and compartmentalization of receptors as well as ligand-receptor interactions play critical means of controlling the molecular structures, and activities of receptors, and thus signaling of cells. In mechanical signaling that senses and responds to physical properties of extracellular environments, mechanical force resulting from cell-matrix and cell-cell interactions additionally serves as a key regulator of signaling. These spatial, molecular (i.e. ligand-receptor interaction), and mechanical cues often interplay either concurrently or consecutively in many mechanical signaling processes. This enables a vast diversity of signaling outcomes, orchestrating complex multicellular behaviors and functions in developmental, physiological, and pathological processes. Despite our increased understanding of mechanical signaling via recent advances in imaging and force-sensing tools, much is still unknown about the interplay between spatial, molecular, and mechanical cues and how they are integrated to potentiate mechanical signaling. To address this unmet need, my lab develops single-cell perturbation modules based on nanoparticles capable of localizing, visualizing, and mechanically activating mechanosensitive membrane proteins at the single cell or molecule level. The key to our approach is the ability to quantitatively deliver a specific spatial, biochemical, and mechanical cue to any desired location and at any given time. In this talk, I will discuss about design, fabrication, and utility of the nanoprobes as a perturbative tool. I will further discuss about applications of nanoprobe systems to dissect, interrogate, and understand the mechanisms underlying cell-cell communication processes via Notch and E-cadherin.