Abstract Revealing the protein–protein interactions (PPIs) of membrane proteins is as challenging as their structural reconstruction, primarily because the molecular structures and related PPIs of membrane proteins are highly dependent on the bio‐membrane where they are situated. DNA origami offers a platform for manipulating molecules with nanoscale precision. Herein, we used a square‐like DNA origami, refer to as DNA origami rubbing, to map the two‐dimensional distribution of membrane proteins in situ. Through artificial models and cell studies, we correlated the efficiency of barcode recording of DNA origami rubbings with the distance between adjacent proteins, and we observed that the frequency of adjacent proteins mapped by DNA origami rubbings was correlated to the abundance of the bait protein. We demonstrated that the DNA origami rubbing was able to reflect the distribution change of adjacent proteins caused by adding the ligand of bait protein. Our results suggested that the DNA origami rubbing can serve as a powerful tool in the field of protein interactomics.
Tang et al. (2026) studied this question.