Biogenic calcite (CaCO3) crystals, like sea urchin spines, incorporate biomacromolecules and other nanoscale materials while still diffracting x-rays as single crystals. Such composite single crystals represent an interesting class of crystalline materials that can couple high surface areas with high degrees of long-range order. In this presentation, I will focus on several related efforts to understand the role of the solid-liquid interfaces in directing the interaction between nanomaterials and inorganic crystals during growth. First, I will discuss our fluid cell Atomic Force Microscopy (AFM) studies of calcite growth in the presence of polymeric nanoparticles with varying surface chemistries. In this study, we investigated the role of the solid-liquid interface in directing the incorporation of secondary (nanoparticle) phases during crystallization. In a related study, we have coupled confocal fluorescence microscopy with 3D foce microscopy and dynamic force spectroscopy measurements to develop a quantitative model for predicting the incorporation efficiencies of ultrasmall, fluorescent, inorganic nanoparticles with different surface functionalities. The Smoluchowksi-Kramers-Langmuir model contains both a kinetic barrier the particles must overcome as they navigate the interfacial solution structure as well as an equilibrium binding constant upon contact with the crystal surface. Together, these studies are leading to design criteria for synthesizing composite single-crystals with unique structure-property relationships. In addition, insights provided by this work may help to elucidate the formation mechanism(s) and properties of biogenic single crystals with incorporated organic material.