The rational design of protein-based supramolecular architectures requires careful consideration of not only intramolecular structure but also the intermolecular interactions that control their self-association into higher order structures. We are particularly interested in the role of interfacial structure and chemistry in defining the nucleation and growth of these systems and specifically the synthesis of extended two-dimensional protein arrays. While scanning probe microscopy provides an excellent tool for studying these processes in real-time, there is an obvious need for integrated instrumentation that provides correlated analytical capabilities. We report here on the development and implementation of a multi-modal coaxial instrumentation platform that enabled the simultaneous acquisition of spectral, optical, and probe microscopy data. Examples will be drawn from studies of lipid phase transitions and protein assembly into two and three-dimensional architectures.