Dimensional reduction of duplex DNA under confinement to nanofluidic slits

Abstract

There has been much interest in the dimensional properties of double-stranded DNA (dsDNA) confined to nanoscale environments as a problem of fundamental importance in both biological and technological fields. This has led to a series of measurements by fluorescence microscopy of single dsDNA molecules under confinement to nanofluidic slits. Despite the efforts expended on such experiments and the corresponding theory and simulations of confined polymers, a consistent description of changes of the radius of gyration of dsDNA under strong confinement has not yet emerged. Here, we perform molecular dynamics (MD) simulations to identify relevant factors that might account for this inconsistency. Our simulations indicate a significant amplification of excluded volume interactions under confinement at the nanoscale due to the reduction of the effective dimensionality of the system. Thus, any factor influencing the excluded volume interaction of dsDNA, such as ionic strength, solution chemistry, and even fluorescent labels, can greatly influence the dsDNA size under strong confinement. These factors, which are normally less important in bulk solutions of dsDNA at moderate ionic strengths because of the relative weakness of the excluded volume interaction, must therefore be under tight control to achieve reproducible measurements of dsDNA under conditions of dimensional reduction. By simulating semi-flexible polymers over a range of parameter values relevant to the experimental systems and exploiting past theoretical treatments of the dimensional variation of swelling exponents and prefactors, we have developed a novel predictive relationship for the in-plane radius of gyration of long semi-flexible polymers under slit-like confinement. Importantly, these analytic expressions allow us to estimate the properties of dsDNA for the experimentally and biologically relevant range of contour lengths that is not currently accessible by state-of-the-art MD simulations.