Friday, 01 April, 2022

A DNA origami platform for developing modular and tunable biosensors

L. Grabenhorst, M. Pfeiffer, P. Tinnefeld, V. Glembockyte

10.1016/j.bpj.2021.11.2855

For nearly every imaginable relevant biomarker, there exists a protein structure that evolved to bind to it with high affinity and specificity. The suitability of such a bio-interaction for its use in the context of biosensing, however is dictated by the dynamic range and dissociation constant of the interaction. By introducing point mutations in the protein sequence the dissociation constant can be affected, but this process is laborous and does typically not affect the dynamic range, i.e. the steepness of the ligand binding curve which is related to cooperativity in the system. Generally, only few examples of artificially induced, controllable cooperativity exist. Here, we present our progress on developing a more generalizable approach for the construction of biosensors with tunable response. Using the programmable nature of DNA origami technology, we developed a platform that opens up new ways of controlling the binding properties of a biointeraction. By arranging several biointeractions on a dynamic DNA nanostructure, we show that it is possible to shift the concentration range and induce cooperative behavior. This is achieved without modifying the biomolecular interaction itself. Due to the modularity of our approach, we anticipate our technology to be broadly applicable and evolve into a valuable tool for biosensors.