Surface Functionalization of Semiconductor Nanowires for Biological Applications

Natural killer (NK) cells play a critical role in the innate immune system by providing immediate response to viruses and pathogens. In addition, NK cells play a major rule in attack tumor and cancer cells. Their cytotoxicity is mediated through a complex mechanism of signal transduction through molecular receptors presenting on the NK cell membrane, which in turn are recognized by corresponding ligands on the membrane of antigen presenting cells (APC). Dendritic cells (DC) are a major part of APC family, are distinct by the high-aspect ratio protrusions in their membrane. Their main function is to bind antigens to their 3D Nanostructure in order to expedite immune response. However, how the immune cell activation is regulated by the 3D organization of NK cell activating ligands and the effect of Nanotopography on NK cells activation is still barely understood.

In this research, we developed bottom-up nanostructures, whose nanomorphology and chemistry mimics the membrane of APC, and used them to study the role of the 3D distribution of the ligands in the immune activation of NK cells. First, we produced the nanotopography form the bottom-up, through ZnO nanowires grown by CVD method and used VLS technique. Then, we added a chemical component to our biomimetic Nanosystems by functionalizing the ZnO nanowires with MHC class I polypeptide-related sequence A (MICA) ligands, which specifically recognize activating receptors NKG2D. For this purpose, we used immobilized in the nanowires Thiol-molecules terminated with Nitrilotriacetic acid, followed by its chelation with Ni and conjugation of Histidine -MICA.

We used fluorescence microscope to image the morphology of NK cells plated on the functionalized nanowires, and the secretion of CD107 – a functional marker for the identification of NK cytotoxic activity. We found that both the Nanotopography and chemical modification with MICA plays a critical in for the immune activity of NK cells.