Researchers are constantly expanding their arsenal of methods to decipher the spatial organization of biological structures. Using microscopes, they can now visualize individual macromolecular components within DNA, protein, or other complexes. However, this resolution typically requires sophisticated equipment applied to specially-processed samples, and it is difficult to simultaneously watch many types of molecules, especially at high density and throughput, or dynamic interactions.

Circumventing the need for expensive microscopes, some recent biochemical approaches attach barcoded DNA probes to molecular targets and then fuse those in nearby pairs together, often by DNA ligation. These DNA “records” are later read out for analysis.

Because these methods destroy the DNA probes in the process of pairing, however, the information acquired from each molecular target cannot include more than one interaction, neither multiple at once nor one changing over time. Such methods can severely limit the quality of any subsequent computational reconstruction, and make reconstruction of individual complexes impossible.

To overcome these limitations, a team at Harvard’s Wyss Institute of Biologically Inspired Engineering led by Core Faculty member Peng Yin, Ph.D., has now developed a DNA nanotechnology-based method that allows for repeated, non-destructive recording of uniquely barcoded molecular pairings, rendering a detailed view of their components and geometries.

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