Surface-Patterned DNA Origami Rulers Reveal Nanoscale Distance-Dependency of the Epidermal Growth Factor Receptor Activation

Over the last two decades, DNA origami has evolved into a well-established, versatile method for the specific arrangement of molecules in the nanometre range.
Within the framework of MOSAIC (Multiscale Origami Structures as Interfaces for cells), we structure DNA-Origami on a surface, to form micro arrays for the analysis of biological processes Here, we focus on the phenomenon of receptor clustering, when the specific grouping of a set of receptors can amplify the sensitivity of a signaling response. With the complete control over the number and spatial arrangement of ligands bound on DNA-Origami at a lower nanoscale, MOSAIC is a compelling way to study this process in detail. The easy adaptability of the origami system allows a wide range of spatial arrangements and ligand-receptor relationships to be investigated.
For MOSAIC, we prepare a glass surface with an oligonucleotide pattern via polymer pen lithography (PPL). DNA origami structures are then applied to glass surfaces using DNA-directed immobilisation (DDI) and decorated with epidermal growth factor (EGF) in various arrangements. In the further course, the specific activation of EGFR in adherent MCF7 cells can be investigated. ... mehrThe focus lies on different intensities of activity and how these can be influenced by the spatial arrangement of EGF on DNA origami structures.
MOSAIC combines a variety of innovative technologies such as DNA origami, PPL and DDI to investigate fundamental aspects of early-stage cell signalling in living cells.