DNA-based materials are ready to become the next nanodiagnostics

DNA-based nanomaterials have gathered intense scientific interest over the past decade and mature more and more into tools that enable researchers to unravel longstanding questions in fundamental molecular biology thanks to their unprecedented spatial control for arranging functional biomolecules. The ability to position bioactive ligands on a surface with nanometer precision and accuracy is a unique feature of DNA-based material platforms. Professors Maartje Bastings (PBL, IMX, EPFL) and Ralf Jungmann (MPIB, LMU) joined efforts to bring this engineering platform to new heights. Bastings explains: "Now that general stability challenges of these structures in biological environments have been overcome, we expect to see the field veer toward exciting applications in nanomedicine within the next decade."

One important question in the field related to the molecular design and stability of these structures has been left unaddressed to date: Are specific DNA extensions used for spatial biofunctionalization still accessible after a protective coating is applied?A negative answer would have put a significant halt on the advancements of DNA-based materials towards applications in nanomedicine.

Jungmann comments: "In this manuscript, we present an in-depth analysis of the accessibility of functional sites on these structures both in the absence and presence of protective coatings. Via DNA-PAINT super-resolution imaging, we can analyze strand accessibility on the level of single handle sites and are able to reliably confirm that all sites remain accessible."

Using a novel, flat and rigid disk-like DNA structure designed by EDBB doctoral student Alice Comberlato, co-first author of the study, the team demonstrated that orthogonal faces can be simultaneously imaged with identical kinetics and strand accessibility, an important prerequisite for cellular interaction studies. Additionally, Alexandra Eklund, co-lead author and PhD student in the Jungmann group, could visualize both top and bottom faces of the structure with sub-10-nm axial resolution and confirm that kinetics are unaltered in the presence of protective coating.

Taken together, this collaborative work presents a strong basis for the development of future strategies in nanomedicine and molecular diagnostics, where structural stability and precise functionality are imperative.