Unraveling the complexity of the macroscopic world based on molecular level details relies on understanding the scaling of single molecule interactions towards integral interactions at the meso- and macroscopic scale. Here, we discuss how one can decipher the scaling of individual single binding interactions at solid/liquid interactions towards the macroscopic level , where a large number of these bonds interacts simultaneously. We developed a synergistic experimental approach combining Surface Forces Apparatus (SFA) experiments and single molecule force spectroscopy (SMFS). We show that equilibrium SFA measurements scale linearly with the number density of a model acid-base bond at an interface, providing acid-amine interaction energies of 10.9 ± 0.2 kT. Using Bell-Evans theory together with Jarzynski’s equality, we can demonstrate how a set of single molecule interaction forces measured by SMFS similarly converges to an interaction energy of 11 ± 1 kT, with unbinding energy barriers of 25 kT ± 5 kT. This indicates excellent predictive power of our newly developed scaling approach.
In addition, we tested a number of other bonds including hydrophobic, ligand-receptor and metal-polymer bonds with our model and find that our model is widely applicable. Hence, we will discuss in detail how single molecule unbinding energy landscapes can be utilized to predict scenarios where a large number of molecules simultaneously interact, giving rise to both macroscopic equilibrated and non-equilibrated interaction energies during adhesive failure. As such, our experimental strategy provides a unique framework for molecular design of novel functional materials through predicting of large-scale properties such as adhesion, self-assembly or cell-substrate interactions based on single molecule energy landscapes.
 S. Raman et al. in Nature Communications, 5 (2014), 5539.
 T. Utzig et al. in Langmuir, 31(9) (2015), 2722.