Intracellular Action of DNA-based Nanomaterials
In the InActioN project, we aim to use DNA-based nanomaterials inside cells, in order to investigate molecular mechanisms within our immune system. Using DNA as a synthetic material offers the unique opportunity to precisely control the spacing of functional molecules like proteins or antibodies. One of the main advantages of using DNA as a material platform is that the components are encoded by natural DNA base pairing, with the result that all architectures are automatically perfect clones of one another. This uniformity is critical when studying interactions with biology, especially when we want to investigate how the number of interactions, or the geometric pattern how these interactions are made, play a role in the biological outcome. These questions can help us to gain a deeper understanding of how materials can interact with biology and how to better design therapeutics, diagnostics or even vaccines.
A critical requirement in order to interact with cellular mechanisms inside the cell, is a stable and controlled intracellular delivery of these nanomaterials. Naturally, DNA is found only in a cell nucleus, and cells have mechanisms in place to destroy what they see as foreign DNA when it is found outside the nucleus. Previous work has focused on the development of protective coatings, however, the impact of this coating on cell uptake had not been carefully analyzed. We are systematically increasing our fundamental understanding of DNA-cell interactions, and utilising this progress to engineer smart solutions to precise communication with natural processes inside the cell.
Our research encourages a shift in materials engineering, by showing that the geometry and flexibility of a material at the nanoscale can have a significant impact on the selectivity of its interactions. While we already demonstrated that uniform, precisely engineered materials can be used to provoke a specific immune response, this project holds a much wider relevance. Engineering a balance of geometry and flexibility for selective interactions is relevant for all molecular interfaces, from crystal self-assembly to biological function. As such, the fundamental guidelines of selective interactions at interfaces opens up a whole new platform of material design for nano-technology.
