A DNA nanoscope via auto-cycling proximity recording

Nat Commun. 2017 Sep 25;8(1):696. doi: 10.1038/s41467-017-00542-3.

Abstract

Analysis of the spatial arrangement of molecular features enables the engineering of synthetic nanostructures and the understanding of natural ones. The ability to acquire a comprehensive set of pairwise proximities between components would satisfy an increasing interest in investigating individual macromolecules and their interactions, but current biochemical techniques detect only a single proximity partner per probe. Here, we present a biochemical DNA nanoscopy method that records nanostructure features in situ and in detail for later readout. Based on a conceptually novel auto-cycling proximity recording (APR) mechanism, it continuously and repeatedly produces proximity records of any nearby pairs of DNA-barcoded probes, at physiological temperature, without altering the probes themselves. We demonstrate the production of dozens of records per probe, decode the spatial arrangements of 7 unique probes in a homogeneous sample, and repeatedly sample the same probes in different states.The spatial organisation of nanostructures is fundamental to their function. Here, the authors develop a non-destructive, proximity-based method to record extensive spatial organization information in DNA molecules for later readout.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism
  • DNA Probes / chemistry
  • DNA Probes / genetics
  • Models, Molecular
  • Nanostructures / chemistry*
  • Nanotechnology / instrumentation*
  • Nanotechnology / methods*
  • Nucleic Acid Conformation
  • Streptavidin / chemistry
  • Streptavidin / metabolism
  • Thermodynamics

Substances

  • DNA Probes
  • DNA
  • Streptavidin