Capturing and Stabilizing Folded Proteins in Lattices Formed with Branched Oligonucleotide Hybrids

The encapsulation of folded proteins in stabilizing matrices is one of the challenges of soft‐matter materials science. Capturing such fragile bio‐macromolecules from aqueous solution, and embedding them in a lattice that stabilizes them against denaturation and decomposition is difficult. Here, we report that tetrahedral oligonucleotide hybrids as branching elements, and connecting DNA duplexes with sticky ends can assemble into materials. The material‐forming property was used to capture DNA‐binding proteins selectively from aqueous protein mixtures. The three‐dimensional networks also encapsulate guest molecules in a size‐selective manner, accommodating proteins up to a molecular weight of approximately 159 kDa for the connecting duplex lengths tested. Exploratory experiments with green fluorescent protein showed that, when embedded in the DNA‐based matrix, the protein is more stable toward denaturation than in the free form, and retains its luminescent properties for at least 90 days in dry form. The noncrystalline biohybrid matrices presented herein may be used for capturing other proteins or for producing functional materials. DNA lattices capture proteins: Three‐dimensional networks of branched oligonucleotide hybrids and connecting duplexes encapsulate proteins up to 159 kDa in size and prevent the denaturation of GFP.