A 6-nm ultra-photostable DNA FluoroCube for fluorescence imaging

Photobleaching limits extended imaging of fluorescent biological samples. We developed DNA-based ‘FluoroCubes’ that are similar in size to the green fluorescent protein, have single-point attachment to proteins, have a ~54-fold higher photobleaching lifetime and emit ~43-fold more photons than single organic dyes. We demonstrate that DNA FluoroCubes provide outstanding tools for single-molecule imaging, allowing the tracking of single motor proteins for >800 steps with nanometer precision. DNA-based FluoroCubes are ~6 nm small, monovalent probes that contain six organic dyes, which confer dramatic photostability relative to single dyes and offer more uniform signal compared to quantum dots for extended biological imaging.