Tip-Enhanced Raman Spectroscopy of RNAs

Tip-enhanced Raman spectroscopy (TERS) has been widely used for the nanoscale chemical and structural analysis of biomolecules. TERS combines indeed the high molecular sensitivity of Raman spectroscopy with the high spatial resolution of scanning probe microscopies (SPM), by exploiting the intense electromagnetic field generated at the apex of a metal SPM tip at nanometer distance from the sample. While TERS studies on ribonucleic acid (RNA) nucleobases started more than two decades ago, several major scientific advances like the advent of a compelling TERS-based RNA sequencing method and the description of amyloid-like RNA-induced tau fibrils potentially implicated in Alzheimer's disease have been only achieved recently. In this chapter, after presenting these promising advances, we provide technical and methodological information allowing TERS maps of such RNA samples to be obtained, processed, and correctly interpreted in order to properly describe the chemical composition of RNA components and the structure of tau proteins interacting with them.