Protein‐DNA Competition at the Bio‐Nano Interface: Structural and Biological Insights From Graphene Oxide Coronas

Abstract Understanding interactions between nanomaterials and biomolecules is essential for advancing biomedical nanotechnologies. This study investigates how double‐stranded DNA of varying sizes affects the protein corona (PC) surrounding Graphene Oxide (GO) nanosheets in DNA‐supplemented human plasma. The findings reveal that DNA plays a pivotal role in modulating the PC composition through dynamic competition governed by factors like surface charge, affinity, and DNA fragment size. At lower DNA concentrations, competition between DNA and proteins for binding sites on GO leads to a corona predominantly composed of proteins, with some DNA molecules also bound. However, as the DNA concentration increases beyond a threshold, a shift occurs. DNA increasingly outcompetes proteins for binding sites, resulting in a two‐component corona enriched with both DNA and proteins. Notably, the proportion of DNA within the corona progressively increases with rising DNA concentration, while the protein content decreases. This dynamic interplay between DNA and proteins has significant biological implications. A monotonic increase in Toll‐like receptor 9 (TLR9) activation is observed as the DNA content within the corona increases. As the corona composition and its influence on cellular responses are crucial, this study emphasizes the relevance of exploring competition at the bio‐nano interface for the advancement of these applications.