Enhanced surface nano-analytics of transient biomolecular processes

Abstract

The study of the physical and chemical properties of biomolecules enables the characterisation of fundamental molecular processes and mechanisms in health and disease. Bulk and single-molecule analytical methods provide rich information on biomolecules, but often require high concentrations and sample preparation away from physiologically relevant conditions. Here, we present the development and application of a lab-on-a-chip approach which combines rapid sample preparation, mixing and deposition to integrate with a range of nano-analytical methods in chemistry and biology, providing enhanced sensitivity and single molecule resolution. We demonstrate that this method empowers multidimensional study of heterogenous biomolecular systems in physiological buffers and concentrations over multiple length scales by nanoscopy and vibrational spectroscopy. We illustrate the capabilities of this platform by capturing and analysing the structural conformations of transient oligomeric species formed at the early stages of the self-assembly of -synuclein, which are associated with the onset of Parkinsons disease. TEASERMaintaining the heterogeneity and structural integrity of monomers and oligomers enables their quantitative study.