How viral shape can inspire the design of optical nanoprobes for investigating nanoparticle-cell interactions

This proposal seeks to develop optical nanoprobes that can investigate particle-cell interactions in real time and at the single-particle level. For this fundamental work, we propose to compare how nanoparticle shape affects binding to cell membranes that express transmembrane receptors. Shape and the expressed ligands on viruses are known to enhance cell invasion. If nanoparticles can be designed with similar attributes, then such novel probes make possible the potential to track particle-cell events as well as improve the design of drug delivery vectors. As a model, we propose to focus on gold nanostars (AuNS) that can have different numbers of defined branches and lengths for comparison. This platform is ideal since (1) the branches taper to sizes similar to proteins (2 nm); and (2) probe features with sizes similar to the length scales for biological interactions can produce more sensitive information. To visualize these probes, we propose to develop a live-cell, multi-channel differential interference contrast (DIC) microscope. As a model study, we will focus on how particle shape and branch numbers of AuNS influences binding to a transmembrane protein target on plasma membranes.