PME Distinguished Colloquium: Dr. Ying Samuel Hu, UIC

Mapping immune cell membranes using a single-molecule lens



The intricate network of immune cells and diverse biomolecules that summon, rile, calm, and transform these cells create a complex puzzle. Solving this puzzle requires sensitive tools at the molecular and nanoscale level. In this talk, I will present our development of unique single-molecule and superresolution techniques and applications of these techniques to study specialized membrane structures of immune cells. I will introduce a new superresolution technique using single-molecule labeling. We successfully demonstrated this technique using several labeling agents, including full-length antibodies, antibody fragments, a bicyclic heptapeptide, and semiconductor quantum dots. The new imaging capability allows us to super-resolve mechanically fragile membrane structures. We discovered a massive membrane fiber network that dendritic cells (DCs) utilize for antigen uptake. We further super-resolved filamentous actin (F-actin) in these membrane fibers and discovered their prevalence in immature DCs. Treating DCs with lipopolysaccharide, a potent stimulator, reduced actin-associated membrane fibers. In addition, F-actin spatially rearranged into more defined cytoskeletal structures near the cortex of mature DCs, suggesting an interplay between F-actin and the plasma membrane in regulating the antigen presentation function of DCs. I will conclude with our recent data suggesting the membrane’s potential involvement in regulating the cytokine release from activated T cells. Together, ultrasensitive imaging techniques provide unique mechanistic insights toward an enhanced understanding of how immune cells communicate through specialized membrane structures, one molecular piece at a time.

Host: Jun Huang