Reconstructing the intrinsic potential energy landscape of interfacial interactions with thermally modulated force spectroscopy

Abstract

Force probes are powerful experimental tools to measure the strength and physical extent of interfacial and intermolecular interactions at nanometer scales. However, because of the stochastic nature of force measurements, most force spectroscopy models require a massive quantity of data in order to obtain meaningful energetic information of the interaction. We developed a force spectroscopy framework based on thermally modulated atomic force microscopy (AFM) force measurements capable of reconstructing energy landscapes of interfacial interactions over 100 nm distances from a handful of force curves. To address the challenge of insufficient sampling at the key points of the interaction, we defined exact equilibrium forces to serve as fiduciary markers that can be used to reliably overlay repeated force curves. The equilibrium force markers create a major advantage in that multiple undersampled force measurements can be compiled as one fully sampled measurement of key regions of two-state binding. The Boltzmann method was directly applied to reconstruct the underlying energy landscape in undersampled regions and combined with the direct integration of the force profile in sufficiently sampled regions to fully determine the energy landscape. We experimentally demonstrate the application of the method to find the intrinsic, continuous force and energy landscape reconstructed along an unprecedented 100 nm distance from merely 15 AFM force curves.