Topologically Engineered DNA Origami: Responsive Locking of DNA Quadrilateral for Biosensing Application

Abstract

DNA nanotechnology offers unique opportunities for creating various accurate and responsive nanostructures. Nevertheless, large-scale conformational changes with high geometric precision and efficiency remain major challenges. Herein we report a topologically engineered DNA origami that undergoes a dramatic transformation from a flexible, shape-indeterminate polygon into a fixed sharply angled rhombus. The DNA quadrilateral nanostructure is first built from a six-helix bundle backbone incorporating three hinge regions to confer mechanical flexibility. Sticky ends at opposing corners are designed as programmable docking domains. A facile catalytic hairpin assembly (CHA) circuit triggered by target miRNA generates duplex lockers that bridge these docking domains, collapsing the DNA quadrilateral into a locked conformation of sharply angled rhombus. Such geometry brings adjacent Cy3−Cy5 couples within the Förster distance. Fluorescence spectra are thus analyzed, which provide a quantitative readout of target miRNA information. A generalizable strategy is established for linking molecular recognition to large-scale DNA nanostructural reconfiguration.