DESCRIPTION: (Applicant's Description) Biomolecular Recognition Using Self-Optimizing Mu1tivalentNanoparticle Receptors Specific recognition of biomolecular Systems is a fundamental goal inbiomedical research. The ability to create efficient receptors for biomolecules allows us to fabricate biosensors that allow real-time monitoring central to the rapid diagnosis of imbalances and illnesses. Recognition of biomacromolecules, including proteins, polysaccharides, and nucleic acids, extends our ability to create diagnostic devices, while also providing an important tool for the modulation of cellularprocesses. To provide a general route for the creation of receptors for small molecules and macromolecules, we have created hosts based on nanoparticle scaffolds. These hosts are readily fabricated from self-assembled Monolayer-Protected Clusters (MPCs), either through direct functionalization during particle formation, or via subsequent place exchangereactions provide Mixed Monolayer Protected Clusters (MMPCs). In preliminary studies, we have demonstrated the ability of MMPCs to efficiently recognize both small molecules and macromolecules. Significantly, these receptors are dynamic, and can be templated through non-covalent interactions. In our proposed research, we will explore the fundamental aspects of these self-optimizing nanoparticle-based receptors, including the effect of monolayer structure, headgroups, and crosslinking on target recognition. Concurrently, we will apply these receptors to the recognition of guests possessing multiple size scales, from small molecule guests to peptides and protein surfaces. We will also explore the recognition of cellular structures, and the use of this recognition for both imaging and therapeutic applications.