We report results of our recent efforts to develop nano-tools to study proteins and their interactions in complex environments that exist on the cell membrane and inside the cells. Due to the spatial constraints imposed on the mobility of cell constituents, it is reasonable to expect that the nature and dynamics of the biomolecular interactions in a living cell would be substantially different from those routinely observed in dilute solutions. Nanotechnology has begun to provide tools with which to monitor processes that occur in membranes and intracellular regions. Nano-optics is a rich source of such emerging tools. Tapered optical fibers coated with metallic films can effectively confine excitation light to sub-wavelength linear dimensions and cubic nanometer excitation volumes. This leads not only to a resolution that exceeds the diffraction-limited values, but also to the elimination of the background signal. Thus, highly localized and specific regions of cellular function can be investigated. By immobilizing silver colloidal nanoparticles on such tapered fibers we have also fabricated surface enhanced Raman scattering (SERS) probes. Nanoprobes have been found to enable detection of fluorescent antibody molecules immobilized on a functionalized glass surface and polychromic quantum dots in picomolar solutions. In addition, we have successfully inserted nanoprobes with dimensions of 30-80 nm into both adherent insect and mammalian cells with maintenance of their viability. We summarize our development of optical nanoprobes with the motivation to detect cell-surface and intracellular proteins of the interleukin-5 system in native cellular environments, through quantum dot fluorescence and SERS.
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