Control over interfacial structure and chemistry is of prime importance for a variety of phenomena, including crystal growth and molecular recognition. Accordingly, a study of ordered two-dimensional arrays as interfaces for molecular self-assembly, ranging from the use of functionalized self-assembled monolayers for directing molecular crystal growth to measurements of antigen-antigen binding, has been performed.

Controlled interfacial surface chemistry was demonstrated through electrochemical and spectroscopic studies of ω-functionalized alkanethiols on Au substrates. Spectroscopic evidence of monolayer charge-transfer and hydrogen-bonded complexes suggested that these films may serve as templates for directing molecular crystal growth. This premise was verified by scanning probe and electron microscopy studies that revealed enhanced nucleation rates and oriented crystal growth on these interfaces.

In situ atomic force microscopy studies of the electrochemical growth of the charge-transfer salt bis(ethylenedithiolo)tetrathiafulvene-triiodide (ET₂I₃) on thermally treated graphite revealed that epitaxial growth of a monolayer mimicking the (001) face of the superconducting β-ET₂I₃ polymorph predominated on open terraces and was suppressed in isolated "molecular corrals". The observation of grain boundary formation within contiguous "corrals" suggested multiple independent nucleation events and illustrated the spatial requirements for nuclei stabilization.

A study of the self-assembly of insulin, a peptide hormone, represents an extension of the aforementioned small molecule studies. The observation of layer-by-layer growth, in combination with molecular scale resolution of the growing (001) face, demonstrated that insulin crystallization likely occurs via self-assembly of hexameric insulin aggregates. Force measurements performed using AFM tips and mica substrates modified with photoactive insulin derivatives revealed a significant reduction in the insulin dimerization forces upon introduction of anti-insulin antibodies, consistent with the correct orientation of the substrate-bound insulin molecules for dimer and anti-insulin complex formation. Differentiation between specific and non-specific binding forces has implications for the fields of molecular and structural biology as well as pharmacology.

These studies have demonstrated that two-dimensional arrays represent a rational means of systematically deconvoluting and identifying the role of specific binding, recognition and epitaxial relationships in molecular self-assembly.