SUMMARY

Energy landscape theory provides the most comprehensive description for all the physical, chemical and biological interactions. However, there are few experimental methods capable of directly measuring the energy landscape of specific interactions. Force probes are the one experimental tool to measure the strength and physical extent of interfacial and intermolecular interactions at nanometer scales or level of single molecules. However, the stochastic nature of force measurements require a massive quantity of data in order to obtain meaningful energetic information of the interaction. Moreover, existing models often presume the shape of the energy landscape thus preventing the experimental probing of complex interactions with multiple binding/unbinding steps.
The goal of this research is to enable full reconstruction of energy and force landscape of arbitrary interactions at single-molecular/nanometer scale. In order to understand the fundamental physics of interfacial and intermolecular interactions, a comprehensive framework to describe force spectroscopy without presumed models is developed. In this thesis, I will apply this framework to Develop a thermally modulated force spectroscopy (TM-FS) technique utilizing white-noise excitation to create cantilever’s fluctuation that is similar to high equivalent temperature. Along with a Boltzmann based equilibrium analysis, I will demonstrate the method can reconstruct the underlying energy landscape of strong, single-well interactions. Secondly, I will implement a variety of probe excitations under selected bandwidth to improve the efficiency of white-noise excitation and suppress interference from undesired mechanical response. Additionally, based upon simulation, we found that we can selectively enhance specific pathway and sample the otherwise inaccessible regions of the interactions. Thirdly, we will apply the newly developed framework and excitation methods to reconstruct the underlying force/energy landscape of multiple-step interactions.