Viewing of complex molecules of ethidium bromide and plasmid DNA in solution by atomic force microscopy

Tertiary structure changes in plasmid DNA, induced by ethidium bromide inte rcalation, have been observed in aqueous solutions by the use of an atomic force microscope. A relaxed closed circular pBR322 molecule became a positi vely supercoiled complex on the drug binding. The supercoiling always resul ted in an interwound (or a plectonemic) form, but never a solenoidal (or a toroidal) form. A quantitative analysis of the compactness of such supercoi led complexes has been carried out.