Theory suggests that biomolecules interact with surfaces via excluded volume effects, electrostatic effects and the formation of specific chemical interactions. In large part to the near complete lack of tractable experimental systems, however, these theoretical predictions have seen little experimental investigation to date. In response, the focus of this dissertation is three fold: 1) the development of such an experimental system, 2) its use to characterize the extent to which surface-biopolymer and inter-biopolymer interactions modulate the folding free energy of a surface-tethered biopolymer, and 3) the development of predictive models of these effects. To these ends, I have developed an electrochemical method by which to determine the folding free energy of a simple, DNA-stem-loop structure site-specifically attached by one end to a self-assembled monolayer deposited on a macroscopic gold surface.

Using this system I have characterized the folding free energy of the stem loop as functions of the charge on the surface and the density with which the biopolymers are packed onto it. I find that, at high ionic strength and low surface charge, the surface-tethered biopolymer is more stable than the same molecule in free solution. This effect is reversed, however, by either increasing the surface charge or decreasing ionic strength. Motivated by these experimental observations I have developed a theoretical model capturing the thermodynamic effects of surface attachment. This model considers the electrostatic interactions between the biopolymer the surface and the entropic cost associated with the excluded volume effect. In the dilute, low packing density regime (i.e., where inter-polymer interactions are negligible), this model quantitatively recapitulates my experimental results without any open parameters.

At high packing densities, however, inter-polymer interactions become significant and my experimental results begin to deviate significantly from the theoretical predictions. Existing polyelectrolyte brush theories, however, are at least qualitatively consistent with these results.