Surfaces have a profound effect on the mechanical behavior of materials. Our group uses in situ transmission electron microscopy and other characterization techniques to explore these connections across scales. First, I will focus on the effect of surface structure and chemistry on the adhesion and compression of nanoparticles. We use in situ mechanical testing inside of a transmission electron microscope to reveal how surface mechanics and surface chemistry govern properties. Second, I will focus on recent efforts to scale up these insights to predict the performance of large-scale systems. Similar to the role of microstructure in governing bulk performance, we strive to use surface structure to rationally tailor surface performance.