We propose to use sum frequency generation (SFG), near edge X-ray absorption fine structure (NEXAFS) and solid state NMR spectroscopy to explore the structural basis for the control exerted by basic peptides on biosilica morphology. The long-term objective of this research is to elucidate the molecular recognition mechanisms used by proteins to control biomineralization processes. The questions we ask are: What is the structural basis for protein recognition of their native mineral phases? What structural motifs do proteins use to interact with mineral phases, and what amino acid side chains orient proteins at mineral interfaces? Answers to these questions would expand not only our understanding of the role played by proteins in biomineralization, but would also provide clear structure-based principles for the design of biomaterials and biomedical devices. However, due to the difficulties in studying protein structure and function at inorganic solid surfaces, there is still remarkably little known of the molecular structure-function relationships that govern hard tissue engineering by proteins. We know far less about the structures of proteins at biomineral interfaces than we know about the structures of membrane proteins. In this proposal we focus on protein regulation of biosilica morphology. It is widely recognized that proteins regulate formation of silica- based cell walls in diatoms. We propose to use a variety of spectroscopies that we have adapted for use in studying biomaterials, to determine how proteins direct the formation of silica-based nanospheres, nanotubules and other structures.