Nanoconfined DNA: From model system to tool in biological analysis

DNA coils undergo  striking conformational transitions when it is confined to volumes with dimensions smaller than one of the characteristic lengths of the molecule.  We are particularly interested in confinement to channels less than two persistence length wide, and hundreds of microns long.  In these channels, DNA extends to 50 % of its contour length and more, thus establishing a clear connection between location and the linear "genetic address" expressed in base pairs. We can fabricate nanochannel systems with arbitrary configurations in two dimensions using fused silica, and thus are able to directly observe DNA configurations through fluorescence microscopy.

This talk will explore the physics of confined DNA, the application to epigenetic mapping, the interactions of electric fields with DNA, and the dynamic analysis of functional DNA-modifying enzymes.  In particular, we have studies the fluctuation spectrum of nanoconfined DNA, have mapped cytosine methylation levels, histone modification profiles, have discovered that a collapse of DNA in high electric fields that hints at the complete breakdown of linear theory, have studied the migration of DNA through nanochannel systems, have observed single-molecule restriction mapping, have detected DNA at nanoelectrode junctions, and have observed a previously unknown pre-catalytic compaction of DNA by a widely used DNA-binding protein.