Biological materials excel at serving mechanical functions, which may be passive as in structural materials, or dynamic, as in cell motility and adhesion components. Impressively, structural biomaterials such as nacre, bone and wood defy "rule of mixtures" relationships by employing high aspect ratio nanoparticles as building blocks in clever molecular designs. Lack of understanding of the physics of interfaces within nanoparticle assemblies makes it challenging to achieve similar mechanical properties with man-made polymeric materials. In this talk, I will present and overview of the state of the art in the bottom-up analysis of nanoparticle assemblies, touching upon new advances in interface design enabled by molecular and multi-scale simulations, machine learning tools, as well as bioinspiration. As a case study, investigations on thin films and nanocomposites made from renewable cellulose nanocrystals (CNCs) will be presented. Our theory and simulation-based inquiries into three complementary strategies for improving mechanical properties will be discussed. First, I will present analyses that explain how binary mixtures of nanocrystal lengths, and microstructural features such as a twisted plywood (Bouligand) lay-up of nanocrystals yield all-cellulosic transparent films with strength and toughness comparable to mineralized biomaterials. Second, I will discuss an efficient, molecular simulation informed framework for predicting the mechanical response of polymer conjugated (hairy) CNC nanocomposites, revealing interface designs that yield optimality between stiffness and toughness. Finally, I will conclude with an outlook on dynamic interfaces in nanocomposites, specifically examining how basic allosteric principles of catch bonds in proteins could be reduced to simple mechanical models to create nanoparticle linkages with counterintuitive force-dependent kinetics.